WEBVTT 00:00:02.189 --> 00:00:06.589 Defining the autistic phenotypes is not difficult. 00:00:07.269 --> 00:00:09.849 Understanding it and bringing real -life data 00:00:09.849 --> 00:00:13.410 and experiences can bring these autistic phenotypes 00:00:13.410 --> 00:00:19.170 into power. For today's episode, we will cover 00:00:19.170 --> 00:00:23.070 inhibitory neurons and the autistic phenotype. 00:00:23.989 --> 00:00:28.829 You likely know about the excitation and inhibition 00:00:28.829 --> 00:00:33.119 imbalance. In the autistic phenotype, this push 00:00:33.119 --> 00:00:36.700 -pull tactic the central nervous system uses. 00:00:37.679 --> 00:00:41.020 Today's episode is all about those inhibitory 00:00:41.020 --> 00:00:45.600 neurons. In addition, we've discussed the thalamus, 00:00:46.240 --> 00:00:50.960 our major hub for sensations, awe. Sensations 00:00:50.960 --> 00:00:54.219 will hit the thalamus and it will continuously 00:00:54.219 --> 00:00:57.679 provide information in a feed -forward feedback 00:00:57.679 --> 00:01:02.200 loop. to the rest of the brain. The thalamus, 00:01:02.399 --> 00:01:05.719 because of its massive role, has a specialized 00:01:05.719 --> 00:01:11.019 shell evolution has equipped it with. Imagine 00:01:11.019 --> 00:01:16.560 perceiving every sense coming in. You can't. 00:01:16.739 --> 00:01:20.980 You don't. And I suspect you wouldn't want to. 00:01:22.079 --> 00:01:25.980 The thalamus has a special feature that appears 00:01:25.980 --> 00:01:29.379 to evolve alongside with more complex behavioral 00:01:29.379 --> 00:01:34.200 species. In humans, this is called the dynamic 00:01:34.200 --> 00:01:39.799 reticular nucleus, or TRN. Now, because humans 00:01:39.799 --> 00:01:42.239 are humans and scientists are scientists, you 00:01:42.239 --> 00:01:44.819 can see this abbreviated slightly different, 00:01:45.359 --> 00:01:48.920 but it is the reticular nucleus. Don't get this 00:01:48.920 --> 00:01:52.040 confused, however, with areas of the brain stem 00:01:52.040 --> 00:01:56.140 that create the so -called reticular formation. 00:01:56.420 --> 00:01:59.969 These are two different things here. The thalamic 00:01:59.969 --> 00:02:03.890 reticular nucleus is a shell, a thin layer of 00:02:03.890 --> 00:02:08.430 inhibitory neurons protecting what enters, what 00:02:08.430 --> 00:02:12.689 signals enter the thalamus. It's a sensory gate 00:02:12.689 --> 00:02:17.189 system. Now hopefully you can understand the 00:02:17.189 --> 00:02:21.770 connection of schizophrenia and autism. The visualization 00:02:21.770 --> 00:02:26.069 and these heightened senses that we have both 00:02:26.069 --> 00:02:30.490 have both schizophrenia and autism. have an excitation 00:02:30.490 --> 00:02:36.210 and ambition imbalance. The outside world is 00:02:36.210 --> 00:02:41.189 chaotic and understanding eye gaze is not complicated. 00:02:41.969 --> 00:02:44.750 Once you understand how those early eye areas 00:02:44.750 --> 00:02:49.069 for visualizing are in heightened waves such 00:02:49.069 --> 00:02:54.069 as gamma compared to so -called normal that are 00:02:54.069 --> 00:02:59.150 in alpha and beta and slight transient shifts 00:02:59.150 --> 00:03:04.550 into gamma, all while being able to inhibit noise 00:03:04.550 --> 00:03:09.030 from the background, which is theta. Theta helps 00:03:09.030 --> 00:03:13.050 kind of regulate, it scans the brain and kind 00:03:13.050 --> 00:03:18.469 of helps regulate these waves. See Earl Miller's 00:03:18.469 --> 00:03:24.270 lab at MIT for some of that. Today's episode 00:03:24.270 --> 00:03:28.099 is all about autistic brainwave phenotype. and 00:03:28.099 --> 00:03:31.840 the gamma power, synchrony, with this EI imbalance, 00:03:32.479 --> 00:03:35.539 and the sensory -cognitive disassociation with 00:03:35.539 --> 00:03:40.099 the autistic phenotype. So let's get into the 00:03:40.099 --> 00:03:44.659 types of inhibitory neurons and their characteristics 00:03:44.659 --> 00:03:48.979 and roles. But first, what do the inhibitory 00:03:48.979 --> 00:03:54.939 neurons do? Where do they go? GABA has three 00:03:54.939 --> 00:03:59.569 receptor types. GABA A, which is ionotropic, 00:03:59.969 --> 00:04:03.490 which is fast. These occur within milliseconds. 00:04:04.770 --> 00:04:09.270 GABA B, which are metabotropic. These are slower. 00:04:09.370 --> 00:04:13.349 These are so -called G -coupled protein receptors. 00:04:14.069 --> 00:04:18.029 These occur, these act within hundreds of milliseconds, 00:04:18.170 --> 00:04:22.670 so they are slower. And a more rare, but still 00:04:22.670 --> 00:04:26.839 important receptor type here is GABA C. which 00:04:26.839 --> 00:04:30.339 is another ionotropic, and these are for sustaining 00:04:30.339 --> 00:04:35.180 the inhibition response, that inactivation, more 00:04:35.180 --> 00:04:40.319 in a tonic -like flow, tonic -like activation. 00:04:40.939 --> 00:04:45.639 These receptors hyperpolarize neurons and modulate 00:04:45.639 --> 00:04:49.759 neural activity with hopes of maintaining EI 00:04:49.759 --> 00:04:53.279 balance. The goal is a balance, but with the 00:04:53.279 --> 00:04:56.759 autistic phenotype. There is a known imbalance. 00:04:57.800 --> 00:05:02.120 Now hard stop here. I said tonic -like. And this 00:05:02.120 --> 00:05:04.079 is true. This is definitely a thing happening 00:05:04.079 --> 00:05:07.100 in the background. Now more recently, we've began 00:05:07.100 --> 00:05:11.100 to talk about waves, these oscillations and frequencies. 00:05:11.839 --> 00:05:14.959 And all of these molecules, these modulators, 00:05:15.519 --> 00:05:19.699 dopamine, serotonin, these excitation inhibition, 00:05:19.779 --> 00:05:23.100 et cetera, norepinephrine. All of these are released 00:05:23.100 --> 00:05:28.120 in different types of kind of frequencies outside 00:05:28.120 --> 00:05:32.420 of the alpha, beta, gamma, and so forth. These 00:05:32.420 --> 00:05:37.899 are called tonic firing, burst firing, and phasing. 00:05:38.980 --> 00:05:43.240 Now tonic is more regular single isolated spikes 00:05:43.240 --> 00:05:47.160 that are in proportion to signals coming in. 00:05:47.459 --> 00:05:50.920 It's a steadier state in the background. and 00:05:50.920 --> 00:05:54.300 this can be used to track changes and reward 00:05:54.300 --> 00:05:58.360 value such as those internal calculators anytime 00:05:58.360 --> 00:06:02.720 you expose or experience a stimuli how does these 00:06:02.720 --> 00:06:06.540 things kind of shift the delta of these so you 00:06:06.540 --> 00:06:10.540 can track the tonic burst and phasic along with 00:06:10.540 --> 00:06:16.339 the the beta gamma and so forth the other one 00:06:16.339 --> 00:06:20.399 is burst firing It is just exactly what it sounds 00:06:20.399 --> 00:06:23.959 like it is. They are bursting high frequency 00:06:23.959 --> 00:06:27.399 and rapid succession. They are short clusters 00:06:27.399 --> 00:06:30.899 of action potentials and they are stronger with 00:06:30.899 --> 00:06:34.839 more potent effects. Now an easy example here 00:06:34.839 --> 00:06:39.199 is like doing a drug. If you do like let's say 00:06:39.199 --> 00:06:41.139 methamphetamine or something you're going to 00:06:41.139 --> 00:06:44.800 get a high bursting action of dopamine. Don't 00:06:44.800 --> 00:06:49.819 do that though. Phasic. is more of a pattern 00:06:49.819 --> 00:06:53.920 of firing that alternates bursts and pauses of 00:06:53.920 --> 00:06:57.639 activity. These signals are transient or more 00:06:57.639 --> 00:07:00.879 so -called moment -to -moment changes. And this 00:07:00.879 --> 00:07:03.980 is also used to allow those internal calculators 00:07:03.980 --> 00:07:07.360 to evaluate things that are happening in the 00:07:07.360 --> 00:07:11.639 environment, like reward or value, conflict, 00:07:11.879 --> 00:07:16.199 and certain outcomes. More event -related than 00:07:16.199 --> 00:07:19.490 tonic. these are all very fascinating things 00:07:19.490 --> 00:07:24.029 and very relevant okay we'll hit on those a little 00:07:24.029 --> 00:07:27.310 bit as we move through the episode but remember 00:07:27.310 --> 00:07:31.029 we have GABA A which are very fast acting GABA 00:07:31.029 --> 00:07:36.410 B slower acting still fast but slower and then 00:07:36.410 --> 00:07:42.670 GABA C which is kind of rare so in the autistic 00:07:42.670 --> 00:07:46.129 phenotype these dysfunctions will drive sensory 00:07:46.220 --> 00:07:50.259 hypersensitivity, cognitive and social deficits, 00:07:51.199 --> 00:07:54.180 and repetitive behaviors. Things that you understand 00:07:54.180 --> 00:07:56.819 about the autistic phenotype. But we're going 00:07:56.819 --> 00:08:00.300 to help explain these so -called phenotypes a 00:08:00.300 --> 00:08:04.019 little bit better. With the specific neuron type, 00:08:04.839 --> 00:08:07.579 certain brain regions and receptor interactions, 00:08:07.579 --> 00:08:12.060 and then just general autistic phenotype problems. 00:08:14.160 --> 00:08:17.180 Now I want to go back before even the central 00:08:17.180 --> 00:08:20.480 nervous system is created and maybe go upstream 00:08:20.480 --> 00:08:22.860 here and something that we've mentioned before 00:08:22.860 --> 00:08:26.920 in the two part neural relation episodes and 00:08:26.920 --> 00:08:31.319 that is a fun sonic hedgehog gene and protein. 00:08:31.319 --> 00:08:37.120 It's called sonic hedgehog not sonic the hedgehog. 00:08:38.019 --> 00:08:40.320 Before the central nervous system is forming 00:08:40.320 --> 00:08:45.960 sonic hedgehog and it's Mesodermal cells will 00:08:45.960 --> 00:08:49.919 signal to the ectoderm to create neuroepithel. 00:08:50.600 --> 00:08:53.000 Neuroepithel is the action by which the central 00:08:53.000 --> 00:08:55.980 nervous system will kind of come in, kind of 00:08:55.980 --> 00:08:59.559 be formed here. This is the process of the central 00:08:59.559 --> 00:09:03.299 nervous system. Sonic Hedgehog is very responsible 00:09:03.299 --> 00:09:08.379 for differentiation and migration. So remember 00:09:08.379 --> 00:09:11.740 the differentiation. Cells become specialized 00:09:11.740 --> 00:09:15.600 cells. and then they migrate to similar cells. 00:09:15.639 --> 00:09:19.059 They migrate to their area of operation, kind 00:09:19.059 --> 00:09:26.580 of. See also P10, SHNK3, and fibroblast growth 00:09:26.580 --> 00:09:32.179 factors and WNT proteins on this kind of epoch 00:09:32.179 --> 00:09:34.419 that we're talking about. All of those things 00:09:34.419 --> 00:09:37.299 that I mentioned are regions of interest for 00:09:37.299 --> 00:09:41.179 the autistic phenotype during this early embryonic 00:09:41.179 --> 00:09:44.779 development. Now I say most of that to say this 00:09:44.779 --> 00:09:50.059 because this is huge. Sonic hedgehog is critical 00:09:50.059 --> 00:09:56.600 for developing inhibition type neurons and an 00:09:56.600 --> 00:09:59.440 area that we're going to discuss a little bit 00:09:59.440 --> 00:10:02.980 in detail later with that thalamic reticular 00:10:02.980 --> 00:10:09.600 nucleus. Sonic hedgehog is responsible for progenitor 00:10:09.600 --> 00:10:13.269 proliferation here that guides in the cortex 00:10:13.269 --> 00:10:17.330 and the thalamus and it supports maturation and 00:10:17.330 --> 00:10:22.250 synaptic integration here this is huge for the 00:10:22.250 --> 00:10:25.409 thalamic reticular nucleus specifically here 00:10:25.409 --> 00:10:29.669 it is sonic hedgehog established the ventral 00:10:29.669 --> 00:10:34.029 domain and it enforces GABAergic identity which 00:10:34.029 --> 00:10:38.909 are patterns if you knock out sonic hedgehog 00:10:38.909 --> 00:10:41.409 you will see this in research paper they'll have 00:10:41.409 --> 00:10:49.299 two minus signs. It'll say SHH minus minus. The 00:10:49.299 --> 00:10:52.399 rodent or the living organism, whatever they're 00:10:52.399 --> 00:10:57.419 studying, will not develop part of the thalamic 00:10:57.419 --> 00:11:01.320 reticular nucleus. The sonic hedgehog gene and 00:11:01.320 --> 00:11:06.460 protein is responsible completely for developing 00:11:06.460 --> 00:11:12.889 the ventral part of this shell. But it has no 00:11:12.889 --> 00:11:17.629 role with the adult formation. Meaning you can't 00:11:17.629 --> 00:11:22.450 knock it out in an adult model and do anything 00:11:22.450 --> 00:11:27.149 to this reticular nucleus. It's already established. 00:11:28.029 --> 00:11:32.470 So for development, this is vital. And if it's 00:11:32.470 --> 00:11:36.129 impaired, the thalamic reticular nucleus and 00:11:36.129 --> 00:11:39.450 these inhibitory neurons, two different things 00:11:39.450 --> 00:11:43.840 there. are going to be impaired or even missing, 00:11:44.059 --> 00:11:47.539 completely missing. And this is shown with models 00:11:47.539 --> 00:11:52.940 for epilepsy, the autistic phenotype, and schizophrenia. 00:11:54.039 --> 00:11:56.940 One additional thing before we get into the specific 00:11:56.940 --> 00:12:03.340 neuronal types of the inhibition. A former guest, 00:12:03.700 --> 00:12:09.320 Ezekiel Ben Ari, had discovered that GABA during 00:12:09.639 --> 00:12:14.740 embryonic and fetal development during gestation, 00:12:14.919 --> 00:12:20.620 GABA is excitatory. It's not until the birth 00:12:20.620 --> 00:12:26.379 that is shifted to inhibitory. There are certain 00:12:26.379 --> 00:12:30.000 sodium and chloride and potassium, I believe, 00:12:30.179 --> 00:12:32.559 if I remember correctly, interactions that kind 00:12:32.559 --> 00:12:36.600 of guide this. You can check out the episode 00:12:36.600 --> 00:12:40.289 I did with Ezekiel Ben Ari. And in the show notes 00:12:40.289 --> 00:12:43.909 of that episode are all those papers. He explains 00:12:43.909 --> 00:12:47.490 it well and uses a PowerPoint for easy understanding. 00:12:48.409 --> 00:12:51.629 So the first inhibition neuron, we've talked 00:12:51.629 --> 00:12:54.669 about it. We have a whole episode on it and it's 00:12:54.669 --> 00:12:58.710 called parvalbum interneurons. These are the 00:12:58.710 --> 00:13:03.309 most dominant type of inhibition that we have 00:13:03.309 --> 00:13:07.350 in the brain. These are fast spiking and expresses 00:13:07.850 --> 00:13:13.610 Parv albium for rapid calcium buffering. Brain 00:13:13.610 --> 00:13:16.529 regions here for the parv albium interneurons 00:13:16.529 --> 00:13:20.370 are the cerebral cortex, specifically the dorsal 00:13:20.370 --> 00:13:24.549 lateral prefrontal cortex. Remember the spindle 00:13:24.549 --> 00:13:29.070 neuron episode. Humans have, we found clusters 00:13:29.070 --> 00:13:32.809 of spindle neurons. They're very few and hard 00:13:32.809 --> 00:13:35.909 to pick up in the dorsal lateral, those spindle 00:13:35.909 --> 00:13:39.379 neurons. and also the ventromedial prefrontal 00:13:39.379 --> 00:13:43.179 cortex. This is a huge region of interest because 00:13:43.179 --> 00:13:46.200 of its massive connections, bi -directional connections 00:13:46.200 --> 00:13:50.620 to all the neuromodulatory nuclei here, such 00:13:50.620 --> 00:13:54.659 as the acetylcholine, serotonin, dopamine, epinephrine, 00:13:54.679 --> 00:13:57.340 norepinephrine, and so forth. And there's also 00:13:57.340 --> 00:14:00.720 a lot of connections with the subcortical areas 00:14:00.720 --> 00:14:05.019 here. This is a big hub here. And also the orbital 00:14:05.019 --> 00:14:10.009 frontal cortex. primary visual cortex, and the 00:14:10.009 --> 00:14:14.769 primary somatosensory cortex, primary auditory 00:14:14.769 --> 00:14:21.289 cortex, so V1, S1, and A1. Huge, huge for sensory 00:14:21.289 --> 00:14:25.950 processing. In addition, parvoalbum, which is 00:14:25.950 --> 00:14:29.090 an area that we covered in the episode about 00:14:29.090 --> 00:14:33.490 parvoalbum, the interior insula, which is emotional 00:14:33.490 --> 00:14:36.879 interoception. understanding what you're doing 00:14:36.879 --> 00:14:40.500 in the environment, how you're feeling. And also 00:14:40.500 --> 00:14:43.600 the posterior insula, so the insula is loaded 00:14:43.600 --> 00:14:47.539 here. And the ACC, anterior cingulate cortex, 00:14:48.200 --> 00:14:51.379 which is kind of like a similar hub to the ventral 00:14:51.379 --> 00:14:55.039 medial prefrontal cortex. It's a huge internal 00:14:55.039 --> 00:15:00.240 calculator here. The superior temporal gyrus, 00:15:00.559 --> 00:15:03.360 remember the decoding the brain? how reading 00:15:03.360 --> 00:15:06.340 works in autism and dyslexia. We talked a lot 00:15:06.340 --> 00:15:10.220 about the superior temporal gyrus. And lastly, 00:15:11.039 --> 00:15:15.480 the inferior temporal cortex. So, within the 00:15:15.480 --> 00:15:21.100 cerebral cortex alone, parvoalbum has massive 00:15:21.100 --> 00:15:25.600 roles. It's also involved with the hippocampus, 00:15:26.159 --> 00:15:34.259 both CA1 and CA3, and the dentate gyrus, and 00:15:34.259 --> 00:15:39.019 also the striatum, the caudate and putamen, and 00:15:39.019 --> 00:15:42.940 also the nucleus accumbens, so both the dorsal 00:15:42.940 --> 00:15:46.000 and the ventral striatum. We talk a lot about 00:15:46.000 --> 00:15:50.299 the striatum because of the basal ganglia. It's 00:15:50.299 --> 00:15:55.200 a major network here. Parv Albium is, of course, 00:15:55.440 --> 00:15:58.360 involved with the thalamus, the thalamic reticular 00:15:58.360 --> 00:16:03.679 nucleus, and the amygdala. You mostly or probably 00:16:03.679 --> 00:16:08.120 know about the amygdala for fear. Well, I have 00:16:08.120 --> 00:16:12.039 news for you. The days of certain regions responsible 00:16:12.039 --> 00:16:15.480 for certain states, emotions, feelings, and so 00:16:15.480 --> 00:16:20.259 forth is over. We're over that. The amygdala, 00:16:20.340 --> 00:16:24.500 yes, is very involved with fear, but it's also 00:16:24.500 --> 00:16:27.100 involved with much other different opposing types 00:16:27.100 --> 00:16:32.000 of emotions or feelings and actions. It's more 00:16:32.000 --> 00:16:35.340 about neural correlates and pathways and connections 00:16:35.340 --> 00:16:40.500 and networks instead of certain regions. That's 00:16:40.500 --> 00:16:43.720 a very bad misnomer. And hopefully that will 00:16:43.720 --> 00:16:48.100 continue to shift. We'll shift out of that. And 00:16:48.100 --> 00:16:51.240 also, finally, the cerebellum. We've had an episode 00:16:51.240 --> 00:16:56.200 about the cerebellum with Reza Shadmir. And the 00:16:56.200 --> 00:17:00.399 parv albium is helping to modulate purgenji cells. 00:17:02.220 --> 00:17:05.640 So the parvalium will hit on all three of those 00:17:05.640 --> 00:17:11.160 receptors A, B, and C. It will hit GABA -A to 00:17:11.160 --> 00:17:14.960 help modulate pyramidal neurons, which is our 00:17:14.960 --> 00:17:18.819 most dominant excitation type. We'll do a whole 00:17:18.819 --> 00:17:23.900 episode on that. GABA -B receptors for a slower 00:17:23.900 --> 00:17:27.960 inhibition for potassium -calcium channel modulation, 00:17:28.960 --> 00:17:31.240 and the prefrontal cortex, hippocampus, and the 00:17:31.240 --> 00:17:34.480 thalamus. And then finally, and this one will 00:17:34.480 --> 00:17:39.980 make sense, it hits GABA -C for sustained inhibition 00:17:39.980 --> 00:17:43.700 and the thalamic reticular nucleus and the lateral 00:17:43.700 --> 00:17:47.299 geniculate nucleus, one of the first stops for 00:17:47.299 --> 00:17:51.299 vision, and the amygdala and cerebellum. And 00:17:51.299 --> 00:17:56.539 it has a high GABA affinity in these areas. So 00:17:56.539 --> 00:18:01.400 what roles do these have in typical brains? Parvalbium 00:18:01.400 --> 00:18:04.559 drive gamma oscillations for sensory integration 00:18:04.559 --> 00:18:10.039 and attention and working memory, providing somatic 00:18:10.039 --> 00:18:14.140 inhibition to prevent hyper excitability. And 00:18:14.140 --> 00:18:17.539 this is critical for the TRN sensory gating. 00:18:18.119 --> 00:18:21.200 So what is happening with the autistic phenotype? 00:18:22.039 --> 00:18:25.619 The reduced density and function in that dorsolateral 00:18:25.619 --> 00:18:29.079 prefrontal cortex, the anterior insula, which 00:18:29.079 --> 00:18:32.960 is mainly what that episode is about, and V1, 00:18:33.380 --> 00:18:38.440 visual cortex 1, and the TRN impairs gamma oscillations, 00:18:38.740 --> 00:18:43.980 leading to sensory hyper sensitivity. The lack 00:18:43.980 --> 00:18:47.539 of parvalbium here cannot regulate this push 00:18:47.539 --> 00:18:51.700 -pull system. So it creates that imbalance and 00:18:51.700 --> 00:18:55.420 it has massive implications to cognitive integration 00:18:55.420 --> 00:18:59.240 and social deficits. Last thing for now on the 00:18:59.240 --> 00:19:02.900 part of Albion, enter neurons. This imbalance 00:19:02.900 --> 00:19:07.259 contributes to that elevated EI ratio, amplifies 00:19:07.259 --> 00:19:11.279 this brain -derived nootropic factor, excitatory 00:19:11.279 --> 00:19:14.569 enhancement. Okay, this is studied in molecular 00:19:14.569 --> 00:19:18.289 psychiatry in 2017. Decent paper about this. 00:19:18.750 --> 00:19:21.210 We'll say a little bit more about brain -derived 00:19:21.210 --> 00:19:26.950 nootropic factor or BDNF in the excitation episode 00:19:26.950 --> 00:19:31.670 more so. But to recap, the parvalbium interneuron 00:19:31.670 --> 00:19:36.869 is the most dense, should be the most dense of 00:19:36.869 --> 00:19:40.529 all the inhibition type neurons, the inactivators. 00:19:40.829 --> 00:19:47.210 The second most is somatostatin expressing interneuron, 00:19:47.430 --> 00:19:52.789 SOM for short. These are slower firing and provides 00:19:52.789 --> 00:19:56.890 feedback inhibition that target the pyramidal 00:19:56.890 --> 00:20:01.849 neuron dendrites. Brain regions here are the 00:20:01.849 --> 00:20:05.710 cerebral cortex, the dorsolateral, that ventral 00:20:05.710 --> 00:20:09.990 medial, and the orbital frontal in addition to 00:20:09.990 --> 00:20:15.950 the V1, S1, and A1, so those three main sensory 00:20:15.950 --> 00:20:21.769 processing cortexes as well. Anterior and posterior 00:20:21.769 --> 00:20:26.710 insula, and the ACC, the superior temporal gyrus, 00:20:27.089 --> 00:20:29.930 just like the parvoalbeom, but they're less, 00:20:30.329 --> 00:20:34.250 and they're also found in the hippocampus CA1 00:20:34.250 --> 00:20:39.519 and CA3 as well, and the amygdala. More so for 00:20:39.519 --> 00:20:42.160 the social behavior, the basolateral and the 00:20:42.160 --> 00:20:46.220 cortical amygdala. We haven't really parsed out 00:20:46.220 --> 00:20:48.400 these different subdivisions of the amygdala 00:20:48.400 --> 00:20:53.839 too much. Receptors, so it works on all three, 00:20:54.079 --> 00:20:57.799 GABA -A, and depending on which one, A5 or A1, 00:20:57.799 --> 00:21:01.500 A2, it's kind of helped modulating the tonic 00:21:01.500 --> 00:21:06.259 inhibition or the phasic on the dendrites. It's 00:21:06.259 --> 00:21:09.250 mostly acting on dendrites here. GABA -B for 00:21:09.250 --> 00:21:13.349 slow dendritic inhibition, and GABA -C has a 00:21:13.349 --> 00:21:16.769 minor role in the amygdala and hippocampus for 00:21:16.769 --> 00:21:22.710 sustained inhibition. The somatostatin helps 00:21:22.710 --> 00:21:28.390 modulate AMP -A and NMDA activity. Those are 00:21:28.390 --> 00:21:32.349 excitation receptors, the post -synaptic. We 00:21:32.349 --> 00:21:35.789 talked about those in quite detail. in an early 00:21:35.789 --> 00:21:39.430 episode of the podcast, episode four or five. 00:21:39.589 --> 00:21:43.569 I can't remember which one, but those are receptors 00:21:43.569 --> 00:21:48.329 that excitation, excitatory neurons will park 00:21:48.329 --> 00:21:52.910 on, they will connect to. Some general roles 00:21:52.910 --> 00:21:57.410 here for the somatostatin and so -called typical 00:21:57.410 --> 00:22:01.650 brains is regulate dendritic excitatory inputs. 00:22:02.160 --> 00:22:06.059 and modulates synaptic plasticity, for instance, 00:22:06.460 --> 00:22:09.819 long -term protetiation. So we've talked about 00:22:09.819 --> 00:22:12.319 the hippocampus there. That's something that 00:22:12.319 --> 00:22:16.680 it does. And it supports, the somatostatin support 00:22:16.680 --> 00:22:20.859 sensory adaptation. Remember, an overarching 00:22:20.859 --> 00:22:25.079 theme of the autistic phenotype is a lack of 00:22:25.079 --> 00:22:28.460 adaptive responses. We talked about the anterior 00:22:28.460 --> 00:22:32.740 cingulate cortex and the ventral medial prefrontal 00:22:32.740 --> 00:22:37.460 cortex. These are major regions major hubs for 00:22:37.460 --> 00:22:41.720 applying adaptive responses. Remember the social 00:22:41.720 --> 00:22:45.019 world is the most unpredictable and most chaotic 00:22:45.019 --> 00:22:49.700 thing that we do especially for the autistic 00:22:49.700 --> 00:22:55.539 phenotype. The role here for the somatostatin 00:22:55.539 --> 00:22:58.819 in autism what it looks like for the autistic 00:22:58.819 --> 00:23:02.410 phenotype is impaired function in the interior 00:23:02.410 --> 00:23:08.990 insula, hippocampus, and V1. In visual cortex 00:23:08.990 --> 00:23:14.349 1, it reduces tonic inhibition, an amplified 00:23:14.349 --> 00:23:18.269 sensory input that contributes to repetitive 00:23:18.269 --> 00:23:22.210 behaviors. And this is also linked to the brain 00:23:22.210 --> 00:23:25.529 -derived nootropic factor, which helps drive 00:23:25.529 --> 00:23:31.980 the excitatory imbalance. So the third inhibitory 00:23:31.980 --> 00:23:37.140 type of cell here, neuron, is vasoactive intestinal 00:23:37.140 --> 00:23:44.059 peptide VIP interneuron. Some characteristics 00:23:44.059 --> 00:23:49.839 of this is mediates disinhibition by inhibiting 00:23:49.839 --> 00:23:57.079 the SOM and the parvalbium so it inhibits inhibitory 00:23:57.079 --> 00:24:01.950 neurons. Does that make sense? We have this inhibition 00:24:01.950 --> 00:24:07.690 as well. So it shuts off somatostatin neuron 00:24:07.690 --> 00:24:12.009 and the parvalbium neuron. And this will enhance 00:24:12.009 --> 00:24:18.170 the pyramidal activity. Now the pyramidal neuron 00:24:18.170 --> 00:24:22.549 is going to be the major region of interest for 00:24:22.549 --> 00:24:26.210 the excitatory cells. So we'll have a whole episode 00:24:26.210 --> 00:24:29.859 on that. But this is going to be huge for sensory 00:24:29.859 --> 00:24:34.180 integration, sensory processing as well. Some 00:24:34.180 --> 00:24:37.980 brain regions of the VIP, the cerebral cortex, 00:24:38.059 --> 00:24:41.119 the same areas. These are all in the same areas. 00:24:41.859 --> 00:24:45.579 Dorsolateral, ventral medial, visual cortex 1, 00:24:45.880 --> 00:24:50.859 somatostatin 1, and the auditory cortex 1. The 00:24:50.859 --> 00:24:54.680 anterior insula and the ACC, anterior cingulate 00:24:54.680 --> 00:25:01.640 cortex. superior temporal gyrus. The hippocampus 00:25:01.640 --> 00:25:06.240 this time only CA1 for those that really want 00:25:06.240 --> 00:25:10.299 to know and the amygdala the basolateral again 00:25:10.299 --> 00:25:15.420 and this time we're going to find that the vasoactive 00:25:15.420 --> 00:25:18.859 intestinal peptides are also in the central amygdala. 00:25:19.440 --> 00:25:23.279 Now evolutionarily the central amygdala is kind 00:25:23.279 --> 00:25:29.420 of It predates the more lateral areas. It's kind 00:25:29.420 --> 00:25:35.759 of home to innate type of fear. The receptors 00:25:35.759 --> 00:25:39.880 here, GABA A. And this targets the interneurons 00:25:39.880 --> 00:25:43.619 for disinhibition, like we talked about. GABA 00:25:43.619 --> 00:25:47.559 B has a little bit of a role here with indirect 00:25:47.559 --> 00:25:52.250 modulation. And GABA C. It has a minor role, 00:25:52.250 --> 00:25:57.230 again, with the amygdala and hippocampus. Another 00:25:57.230 --> 00:26:01.309 role that it has is expression of VIP receptors, 00:26:02.170 --> 00:26:07.190 which are G -protein coupled, and nicokinetic 00:26:07.190 --> 00:26:12.049 acetylcholine receptors. Now, nicokinetic acetylcholine 00:26:12.049 --> 00:26:15.589 receptors are very, very fascinating. Acetylcholine, 00:26:15.750 --> 00:26:18.690 you might know, is a neuromodulator. It has two 00:26:18.690 --> 00:26:25.480 receptors. Nicokinetic and mucicarnic. The nicokinetic 00:26:25.480 --> 00:26:29.839 receptor, just similar as nicotine, right? You 00:26:29.839 --> 00:26:34.420 know about the nicotine. These are very excitatory. 00:26:34.779 --> 00:26:37.700 These are very excitatory type of excitation. 00:26:39.359 --> 00:26:43.500 So the vasoactive intestinal peptide row in so 00:26:43.500 --> 00:26:47.240 -called typical brains is to facilitate selective 00:26:47.240 --> 00:26:50.559 circuit activation for attention and sensory 00:26:50.559 --> 00:26:54.000 processing. We kind of made sense with that, 00:26:54.000 --> 00:26:57.880 with this inhibition role here, and then how 00:26:57.880 --> 00:27:03.859 it's interacting with the excitation parts. The 00:27:03.859 --> 00:27:07.059 role of the autistic phenotype is an altered 00:27:07.059 --> 00:27:10.599 function in the dorsolateral prefrontal cortex 00:27:10.599 --> 00:27:14.480 in the interior insula disrupts attention and 00:27:14.480 --> 00:27:18.240 social processing, which will then, of course, 00:27:18.559 --> 00:27:23.279 lead to social deficits. And this is a good study 00:27:23.279 --> 00:27:25.579 in Cell Reports. One of my favorite journals 00:27:25.579 --> 00:27:31.039 is Cell Press. And this was done in 2019. Okay, 00:27:31.039 --> 00:27:34.720 so a fourth type of inhibitory neurons. It's 00:27:34.720 --> 00:27:40.920 kind of a two -in -one. Calbindin and calretinin 00:27:40.920 --> 00:27:44.859 expressing interneurons. So why the two -in -one? 00:27:45.099 --> 00:27:48.930 Well, I... Just assume that these are very rare. 00:27:49.309 --> 00:27:53.470 They're not real known. Not studied that much. 00:27:54.289 --> 00:27:57.589 But the characteristics here is the calbindin 00:27:57.589 --> 00:28:01.329 provides dendritic inhibition, which is pretty 00:28:01.329 --> 00:28:06.690 common theme here. Calritinin mediates that disinhibition 00:28:06.690 --> 00:28:12.109 and it targets those interneurons as well. Brain 00:28:12.109 --> 00:28:16.990 regions here for the calbindin. is pretty similar. 00:28:17.130 --> 00:28:20.950 Dorsolateral prefrontal cortex, orbital frontal 00:28:20.950 --> 00:28:27.789 cortex, V1, various layers of S1, layers four 00:28:27.789 --> 00:28:32.309 through six, so very detailed location here for 00:28:32.309 --> 00:28:39.650 S1. Calbondin is also in CA1 and CA3 subdivisions 00:28:39.650 --> 00:28:44.480 of the hippocampus and the dentate gyrus. and 00:28:44.480 --> 00:28:48.480 the amygdala, the basolateral amygdala again 00:28:48.480 --> 00:28:55.220 and the cortical amygdala. The chalretanin is 00:28:55.220 --> 00:28:58.940 in the ventral medial prefrontal cortex so we're 00:28:58.940 --> 00:29:04.440 kind of separating here finally. Visual cortex 00:29:04.440 --> 00:29:09.759 1 and auditory cortex 1 and also the anterior 00:29:09.759 --> 00:29:13.839 insula. and the ACC anterior cingulate cortex, 00:29:14.759 --> 00:29:17.980 and the superior temporal gyrus. There's not 00:29:17.980 --> 00:29:21.279 a whole lot of information to provide on the 00:29:21.279 --> 00:29:24.980 receptors, what they're acting on, why they're 00:29:24.980 --> 00:29:28.380 acting on it. These are not well -known cells 00:29:28.380 --> 00:29:30.759 here that we're talking about. But the roles 00:29:30.759 --> 00:29:34.400 in the typical brains is fine -tuning local circuits 00:29:34.400 --> 00:29:39.000 for sensory and emotional processing and neuroplasticity. 00:29:40.380 --> 00:29:43.059 The role in the autistic phenotype is shown to 00:29:43.059 --> 00:29:46.700 be reduced functioning in the interior insula 00:29:46.700 --> 00:29:50.319 and hippocampus contributes to sensory and emotional 00:29:50.319 --> 00:29:54.740 deficits. Though this is kind of not well studied. 00:29:55.259 --> 00:29:58.380 They're just not well known kind of cell types 00:29:58.380 --> 00:30:01.099 here that we're talking about. But we'll wrap 00:30:01.099 --> 00:30:04.579 it up with the purgenji cell, which is well studied. 00:30:05.160 --> 00:30:08.140 especially in the autistic phenotype. There's 00:30:08.140 --> 00:30:11.519 a major deficit of progeny cells in the autistic 00:30:11.519 --> 00:30:15.920 phenotype. The whole episode with Dr. Reza Shadmir 00:30:15.920 --> 00:30:20.079 is so fantastic. He's such a great human being. 00:30:21.119 --> 00:30:23.519 The characteristics here are these are GABA -urgent 00:30:23.519 --> 00:30:26.640 neurons in the cerebellum only and they provide 00:30:26.640 --> 00:30:31.779 primary inhibitory output. It's for precise motor 00:30:31.779 --> 00:30:36.440 control. Very precise. detail here, fine -tuning 00:30:36.440 --> 00:30:40.920 these purgenji cells are doing. Brain regions 00:30:40.920 --> 00:30:44.940 are the cerebellar, the cortex of the cerebellar, 00:30:45.559 --> 00:30:48.339 and lobules one through five, and they project 00:30:48.339 --> 00:30:53.619 to deep cerebellar nuclei. Receptors here are 00:30:53.619 --> 00:30:58.640 GABA -A for fast inhibition into deep nuclei. 00:30:59.720 --> 00:31:02.859 And then GABA -B for the slower inhibition. Remember 00:31:02.859 --> 00:31:06.839 these are slower type G protein coupled. And 00:31:06.839 --> 00:31:10.559 GABA -C for a sustained inhibition. So more of 00:31:10.559 --> 00:31:15.200 that helping sustain and tonic flowing of granule 00:31:15.200 --> 00:31:22.579 cells. And it also helps receive AMPA and NMDA 00:31:22.579 --> 00:31:27.450 inputs. The role in the typical brain is refined 00:31:27.450 --> 00:31:33.349 motor coordination and cognitive timing in cerebellocortical 00:31:33.349 --> 00:31:37.609 loops. The Burgenji cells here are vastly underrated. 00:31:38.490 --> 00:31:42.569 One of the most underrated cells in the entire 00:31:42.569 --> 00:31:46.349 human brain. And if you don't know, the cerebellum 00:31:46.349 --> 00:31:49.890 is kind of like that miniature brain in the back, 00:31:50.289 --> 00:31:56.029 the posterior ventral back. of the brain. And 00:31:56.029 --> 00:31:58.730 most species have them. If you look at like a 00:31:58.730 --> 00:32:03.170 rat or a mouse, it's at the top. But that's because 00:32:03.170 --> 00:32:07.250 the mouse and rat brain isn't as developed. So 00:32:07.250 --> 00:32:12.329 anatomically, the cerebellum and the rat or mouse 00:32:12.329 --> 00:32:17.390 brain is identical. If you think about the growth 00:32:17.390 --> 00:32:22.269 and evolution versus the human cortex, it's all 00:32:22.269 --> 00:32:28.599 structured the same. just less. For the autistic 00:32:28.599 --> 00:32:33.420 phenotype, the cell loss in vermis. Dr. Shadmere 00:32:33.420 --> 00:32:37.839 talked about this a lot, and Lobules 6 and 7 00:32:37.839 --> 00:32:41.279 disrupt motor and social behaviors and contributes 00:32:41.279 --> 00:32:48.380 to serotypes. So we covered six inhibitory pepsi 00:32:48.380 --> 00:32:52.769 neurons there, quite dense, and the nomenclature 00:32:52.769 --> 00:32:56.329 and roles, brain regions and so forth. So it's 00:32:56.329 --> 00:32:59.309 pretty dense stuff here but very important because 00:32:59.309 --> 00:33:02.450 of the roles of this push -pull tactic system 00:33:02.450 --> 00:33:06.609 that the central nervous system uses. So let's 00:33:06.609 --> 00:33:08.890 talk a little bit more about this push -pull 00:33:08.890 --> 00:33:15.289 system. An EI balance is dynamic interplay between 00:33:15.289 --> 00:33:20.109 activation and inactivation. We use excitatory 00:33:20.109 --> 00:33:24.750 like glutamatergic and these pyramidal neurons 00:33:24.750 --> 00:33:29.130 and inhibitory the GABAergic that we've just 00:33:29.130 --> 00:33:33.210 talked about and this is regulating neural circuitry 00:33:33.210 --> 00:33:38.190 the push side this excitation side the pyramidal 00:33:38.190 --> 00:33:41.869 neurons in the cortex and the thalamus drive 00:33:41.869 --> 00:33:48.230 activity with those AMPA and NMDA receptors and 00:33:48.230 --> 00:33:51.650 this is promoting things like learning and promoting 00:33:51.650 --> 00:33:55.769 sensory and cognitive processing, we must be 00:33:55.769 --> 00:34:00.130 activated to process things. The pull system, 00:34:00.569 --> 00:34:03.950 the inhibition, the things that will help keep 00:34:03.950 --> 00:34:07.670 us in check here, are here to prevent overload, 00:34:08.550 --> 00:34:12.050 hypersensitivity, hyper excitability, and ensures 00:34:12.050 --> 00:34:16.489 precision. This is all about a balance, a healthy 00:34:17.460 --> 00:34:22.619 movement of a seesaw or the bumper rails down 00:34:22.619 --> 00:34:26.940 a bowling alley. This is what excitation inhibition 00:34:26.940 --> 00:34:30.840 is doing. It's trying to keep everything in check, 00:34:31.139 --> 00:34:35.599 in line, in optimal ranges. Okay, before we wrap 00:34:35.599 --> 00:34:38.380 up, I like to think about things from an evolutionary 00:34:38.380 --> 00:34:41.579 standpoint. Why do we have the things that we'd 00:34:41.579 --> 00:34:43.539 have and what are they trying to accomplish? 00:34:44.019 --> 00:34:47.489 What are we supposed to be doing with them? So 00:34:47.489 --> 00:34:51.110 the parv albium interneuron, this is mostly responsible 00:34:51.110 --> 00:34:55.349 to drive gamma oscillations for sensory and cognitive 00:34:55.349 --> 00:34:59.730 synchronization. And it gates sensory inputs 00:34:59.730 --> 00:35:03.170 for that thalamic reticular nucleus, especially 00:35:03.170 --> 00:35:07.250 in the visual somatosensory and auditory sectors. 00:35:07.869 --> 00:35:10.710 We'll parse that out in a different episode now. 00:35:10.949 --> 00:35:14.670 It's too much to add in the thalamic reticular 00:35:14.670 --> 00:35:18.099 nucleus for this episode. It's just too much. 00:35:19.039 --> 00:35:22.820 And it also provides somatic inhibition in the 00:35:22.820 --> 00:35:27.099 cortex and hippocampus. So this is the most dense 00:35:27.099 --> 00:35:30.780 interneuron, inhibitory interneuron I should 00:35:30.780 --> 00:35:35.719 say. The somatostatin interneurons is mostly 00:35:35.719 --> 00:35:40.039 responsible to regulate dendritic inputs. So 00:35:40.039 --> 00:35:44.820 it kind of regulates where cells park on dendrites. 00:35:46.219 --> 00:35:50.820 modulates plasticity and supports sensory adaptation. 00:35:51.559 --> 00:35:54.619 This is a big thing that humans do is adapting 00:35:54.619 --> 00:35:59.780 but specifically in the cortex and the hippocampus. 00:36:01.119 --> 00:36:05.699 The VIP interneurons VIP this facilitates that 00:36:05.699 --> 00:36:09.679 this inhibition for helping to select attention 00:36:09.679 --> 00:36:15.099 in the cortex signal And noise is how neuroscience 00:36:15.099 --> 00:36:19.460 looks at this. Signal to noise ratio. What can 00:36:19.460 --> 00:36:24.960 you quiet? The cow binding and cow retaining. 00:36:25.719 --> 00:36:29.019 These are more for the fine tuning of local circuits 00:36:29.019 --> 00:36:33.300 for the sensory and emotional processing. For 00:36:33.300 --> 00:36:36.840 Genji cells, refine cerebellar motor and cognitive 00:36:36.840 --> 00:36:39.559 output. Remember this is all about precision 00:36:39.559 --> 00:36:44.679 control here. especially with reward, Shadmere 00:36:44.679 --> 00:36:49.659 said. They're mostly involved with highly rewarding 00:36:49.659 --> 00:36:55.480 things. So some evolutionary aspects. In early 00:36:55.480 --> 00:37:00.139 vertebrates, GABAergic interneurons, the parvalbium 00:37:00.139 --> 00:37:03.820 and somatostatin, emerge to stabilize neural 00:37:03.820 --> 00:37:07.780 circuits and prevent seizures even. Now you know 00:37:07.780 --> 00:37:12.400 about autism and epilepsy, for sure. This was 00:37:12.400 --> 00:37:16.880 reviewed in Nature Reviews neuroscience. Mammalian 00:37:16.880 --> 00:37:21.019 expansion. The increased, should be increased 00:37:21.019 --> 00:37:24.860 parvalbium interneuron density. In the thalamic 00:37:24.860 --> 00:37:30.400 reticular nucleus and the cortex support complex 00:37:30.400 --> 00:37:34.599 sensory cognitive processing. Everything we're 00:37:34.599 --> 00:37:40.519 doing in the environment is pretty complex. Primate 00:37:40.519 --> 00:37:44.639 specific. increases in the dorsolateral prefrontal 00:37:44.639 --> 00:37:48.619 cortex and the anterior insula. And this enhances 00:37:48.619 --> 00:37:52.599 social and cognitive functions. That whole episode 00:37:52.599 --> 00:37:57.440 was essentially about this. So lastly, if you 00:37:57.440 --> 00:38:00.280 think about developing, learning to navigate 00:38:00.280 --> 00:38:03.820 the world, learning your environment, how this 00:38:03.820 --> 00:38:07.780 is interacting here and interfering, the translation 00:38:07.780 --> 00:38:14.619 of autism or autist Autistic is autos, A -U -T 00:38:14.619 --> 00:38:20.019 -O -S, which means self. Do you understand why? 00:38:20.780 --> 00:38:26.420 The self is much calmer and even a lot more entertaining 00:38:26.420 --> 00:38:30.900 because of our ability to be present inside. 00:38:31.719 --> 00:38:34.820 The biology that gives us autism allows us to 00:38:34.820 --> 00:38:38.119 be comfortable within our self. And this promotes 00:38:38.119 --> 00:38:42.300 accelerated learning as well. This is very fascinating 00:38:42.300 --> 00:38:45.900 with those visual thinking processes here, which 00:38:45.900 --> 00:38:49.400 is in large part due to that heightened gamma 00:38:49.400 --> 00:38:55.000 activity in those early visual processes. Retina, 00:38:55.440 --> 00:38:58.820 the retina ganglion cells, lateral geniculate, 00:38:59.199 --> 00:39:02.860 and then the superior colliculus and the visual 00:39:02.860 --> 00:39:07.380 cortex V1 through V4. These are all gamma waves. 00:39:07.500 --> 00:39:10.460 These are all heightened. in the autistic phenotype, 00:39:10.980 --> 00:39:13.920 you know about the attention to detail, the inability, 00:39:14.280 --> 00:39:19.119 let's say, to shift off of something. It's not 00:39:19.119 --> 00:39:21.860 that difficult to understand, is it? It's not 00:39:21.860 --> 00:39:24.480 that difficult to understand the autistic phenotype. 00:39:25.219 --> 00:39:28.699 The major problem here is environmental insults. 00:39:28.699 --> 00:39:32.500 People are not understanding it, not understanding 00:39:32.500 --> 00:39:36.360 the autistic phenotype, in large part, I suspect, 00:39:36.900 --> 00:39:40.309 because of them. We love to confirm our bias. 00:39:40.389 --> 00:39:43.329 We love to confirm what we think and how others 00:39:43.329 --> 00:39:49.469 ought to be. This is a huge problem. I have something 00:39:49.469 --> 00:39:52.449 exciting. 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Shapiro launched Chroma to restore 00:42:41.400 --> 00:42:45.500 the natural light lost to screens in indoor living, 00:42:46.559 --> 00:42:50.059 and delivers faster recovery, sharper minds, 00:42:50.079 --> 00:42:54.880 and better sleep. Their products hit hard. The 00:42:54.880 --> 00:42:58.880 Iron Forge speeds muscle repair. with red and 00:42:58.880 --> 00:43:02.659 near -infrared light, while the skylight mimics 00:43:02.659 --> 00:43:08.300 sunlight to boost sleep and energy. A standout, 00:43:08.619 --> 00:43:12.480 the Forge Lamp, is a portable gem that fires 00:43:12.480 --> 00:43:20.019 660 nanometer and 850 nanometer light to energize 00:43:20.019 --> 00:43:25.170 mitochondria and heal tissues on the go. Remember 00:43:25.170 --> 00:43:27.710 the four red -light chromophores on cytochrome 00:43:27.710 --> 00:43:31.570 c -oxidase frequently talked about in the podcast? 00:43:32.289 --> 00:43:36.869 This is why. Their products are built with military 00:43:36.869 --> 00:43:42.889 -grade durability that have lasting impact. Chroma's 00:43:42.889 --> 00:43:48.690 tech fuses precision and power. Gallium titride 00:43:48.690 --> 00:43:52.889 power supplies. Smaller, cooler and stronger 00:43:52.889 --> 00:43:57.070 than silicone. provide flicker -free light that's 00:43:57.070 --> 00:44:01.769 easy on the eyes. High -powered LEDs target key 00:44:01.769 --> 00:44:06.369 wavelengths for skin, tissue, and cellular health 00:44:06.369 --> 00:44:10.150 with smart heat management for the lasting impact. 00:44:11.250 --> 00:44:14.590 Every design decision Chroma makes serves a purpose 00:44:14.590 --> 00:44:19.110 to create devices that are precise, durable, 00:44:19.590 --> 00:44:24.900 and effective for improving human life. Remember, 00:44:25.340 --> 00:44:27.940 humans use different wavelengths of light for 00:44:27.940 --> 00:44:32.840 different functions of life. Remember when I 00:44:32.840 --> 00:44:39.960 ask, what do you think light is? Chroma designs 00:44:39.960 --> 00:44:44.860 with our biology in mind. From sleep aids and 00:44:44.860 --> 00:44:49.539 wound healing to mitochondrial energy, full body 00:44:49.539 --> 00:44:53.010 lights and blue light blocking glasses. They 00:44:53.010 --> 00:44:58.110 are US made and chroma ships globally and accepts 00:44:58.110 --> 00:45:06.769 FSA and HSA payments Use autism at checkout for 00:45:06.769 --> 00:45:12.570 a 10 % off discount That's autism at checkout 00:45:12.570 --> 00:45:17.210 for a 10 % off discount If you're listening to 00:45:17.210 --> 00:45:19.929 the podcast listening to the episode, please 00:45:19.929 --> 00:45:23.409 feel free to leave a review or rating In podcasting, 00:45:23.630 --> 00:45:26.050 reviews, ratings, and downloads are huge and 00:45:26.050 --> 00:45:28.530 I very much appreciate your feedback. You can 00:45:28.530 --> 00:45:34.670 contact me on X at RPS 47586. We can discuss 00:45:34.670 --> 00:45:37.289 anything and everything about autism. I very 00:45:37.289 --> 00:45:40.190 much appreciate your comments and your interactions 00:45:40.190 --> 00:45:43.590 on X. You can check out the YouTube page for 00:45:43.590 --> 00:45:47.110 all the videos, full -length videos, shorts, 00:45:47.190 --> 00:45:56.639 and clips. You can email me info. Thank you for 00:45:56.639 --> 00:45:59.840 listening to From the Spectrum Podcast.