Thoughts regarding the following:
Interesting additional thought about the cholesterol paper: It could explain why “schizophrenia” is late onset. Having “too much” generally isn’t a problem up until post puberty because everything is still in a state of rapid development, it’s not until development starts slowing (or degrading in the case of dementia) that “schizophrenia” (or more specifically the perception disorders associated with it) become a problem.
Man, the mice being self-aware paper is an ethical black hole isn’t it? Hasn’t that been the traditional rationale for using murine models, they aren’t self-aware? Maybe LeDoux can swoop in and explain how they just don’t feel pain like we do using some other construct.
With regard to the astrocyte-neuron model, according to my model (and why I’m discounting weight due to confirmation bias) it suggests that pattern matching happens in the brainstem initially, and either generates a salience pulse on pattern match (triggering instant behavior like the startle reflex), or on no match it kicks it up the stream for the dorsal/ventral valence analysis. It always still gets kicked up, it’s just the lower brainstem handles the instantaneous pattern matching in much the same way as other autonomous functions. This is useful in the context of “PTSD”, where really highly weighted patterns can trigger pretty overwhelming autonomic responses because they are right on the salience source. In this context, think of “PTSD” as a “stuck” pattern which isn’t getting processed and cleared because of it’s weight.
Looking at treatments like EMDR, we are essentially “jiggling” the pattern loose so it can be kicked up (down) the processing chain. One interesting alternative treatment for “PTSD” might be triggering the pattern, then providing stimulation in and around the fourth ventricle. My hunch is that this will “push” it through to the deep cerebellar nuclei and allow the valence processing to actually happen (which isn’t happening normally). There’s a decent amount of support that energizing the fourth ventricle will accelerate glymphatic function, increasing the amount of push or space for the protein/RNA payload to squeeze through.
And yes, I am framing the memory/behavioral response as actual physical particles which can vary in size depending on the “strength” (is this number of synapses it’s encoded to or a measure of methylation change, for example is it because it’s pushing under/over production of protein products or is it because it’s encoded to a lot of sites at once?) of the encoded pattern/engram.
I really wish we had an imaging system that wasn’t based on average, or at the very least more imaging work reported a range of values rather than just the average.
24S-Hydroxycholesterol in Neuropsychiatric Diseases: Schizophrenia, Autism Spectrum Disorder, and Bipolar Disorder – Pretty sure these are all the same thing. Cholesterol is essentially the substrate of memory, it regulates the transfer of particles into/out of cells which are the literal blocks that memory is built upon. Combining this with “the model”, it would imply that “schizophrenia” is “too much transfer”, “autism” is “too little transfer”, and “bipolar” is a really wide homeostasis swing between the two.
Situation-Based Neuromorphic Memory in Spiking Neuron-Astrocyte Network – Huh, interesting flow idea. Pattern match against known, then run against a “two-net” NN. Confirmation bias much? I believe I might be.
Brain-wide circuit-specific targeting of astrocytes – Heh, it’s really interesting that most viruses which impart a noticeable cognitive impact generally tend to selectively target astrocytes. And those which can be found in neurons are usually restricted to the synapse adjacent regions. This is a really cool idea and might be the first real test of the astrocytes as organism wide cognitive co-ordinators conceit.
Glial regulation of critical period plasticity – It’s a review. There are many like it. But this one is not mine (sorry, for the Full Metal Jacket reference). I think most of this is pretty well trodden ground.
Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity – It’s weird to me that the necessary push/pull of components required to maintain homeostasis across a wide variety of environmental conditions isn’t obvious.
RNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms – Back on my “DNA is an artifact of RNA” horse. Spicy, I know.
Visuotactile integration facilitates mirror-induced
self-directed behavior through activation of
hippocampal neuronal ensembles in mice – Ruh Roh Raggy. Ethics iceberg ahead.
How S100B crosses brain barriers and why it is considered a peripheral marker of brain injury – Good primer on why S100b is such a good potential biomarker of a lot of things, however I’d argue it’s way more flexible than even this work asserts. Measuring this should be part of the standard panel of tests done for everyone, we’d be able to see serious issues coming long before they did, even if there’s nothing we can really do about it yet.
Microglia-derived extracellular vesicles in homeostasis and demyelination/remyelination processes – To the “immune system is an equal participant in cognition” conceit.
Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism – This is adjacent to the cholesterol work above, and also ties together the “ADHD is a trauma response” conceit. ARGH, too much confirmation bias today, my brain is getting spooked!
Specialized astrocytes mediate glutamatergic gliotransmission in the CNS – It’s surprising that confirmation of this has been controversial up until recently! How did we assume glia<->glia transmission worked? Pretty big oversight on my part, I didn’t detect a controversy here at all.
Ultrasound Modulates Calcium Activity in Cultured Neurons, Glial Cells, Endothelial Cells and Pericytes – Mechanosensitivity seems universal to all cells.
Astroglial S100B Secretion Is Mediated by Ca2+ Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues – So it looks like S100b is an interface protein between the nucleus and environmental processing part of the cell. S100b issues may indicate an issue processing environment, which is consistent with many of the recent “loss of epigenetic sensitivity” theories of aging.
Associating growth factor secretions and transcriptomes of single cells in nanovials using SEC-seq – Banging the drum again here, but yet another reminder that RNA expression rates does NOT equal protein/peptide expression. There’s a generalized assumption that increases in RNA expression indicates an increase in RNA products, and this assumption is really fouling the hell out of a lot of RNAseq work.
Astrocyte coverage of excitatory synapses correlates to measures of synapse structure and function in primary visual cortex – Complexity of the astrocyte network drives the complexity of the neuron network
Network-level encoding of local neurotransmitters in cortical astrocytes – These guys smell it.
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Alleviates Sepsis-Induced Cardiomyopathy by Inhibiting Pyroptosis – MANF is an odd target, but makes sense. Something about this is ringing an alarm bell though.
Altered expression of inflammation-associated molecules in striatum: an implication for sensitivity to heavy ion radiations – Haha, holy shit. Now this is a test of the immune cognition link I would never have thought of in a billionty years.
Tau here, tau there, tau almost everywhere: Clarifying the distribution of tau in the adult CNS – Yeah, tau particles are the same class of goofery as amyloids.
Resident immune responses to spinal cord injury: role of astrocytes and microglia – If you think about it from a raw processing response, what’s the difference between a sensor in the brain and a sensor anywhere else?
Mechanisms of aquaporin-4 vesicular trafficking in mammalian cells – Aquaporin or what happens when the toilet gets clogged?
Higenamine exerts antidepressant effect by improving the astrocytic gap junctions and inflammatory response – Countdown until the nootropic guys start banging rails of whatever this stuff is in 5, 4, 3, 2…
Reduced Bergmann glial process terminations and lateral appendages in essential tremor – Less glial “smoothing” equals…
Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain – We are always in pain. Astrocytes turn it down/off.
Radial astrocyte synchronization modulates the visual system during behavioral-state transitions – Oh wow. So let me tell you a little story about brainstem astrocytes and downstream functions…
Visualization and Characterization of the Brain Regional Heterogeneity of Astrocyte–Astrocyte Structural Interactions by Using Improved Iontophoresis with Dual-Fluorescent Dyes – Yay, better astrocyte specific tools! This is a pretty big barrier, that most of our tools are only optimized around old conceits of function.
Exposure to Δ9-tetrahydrocannabinol leads to a rise in caspase-3, morphological changes in microglial, and astrocyte reactivity in the cerebellum of rats – Generally increased microglial arborization is bad, it means astrocytes have lost connection and the phagocytes are trying to clear the circuit to reactivate them. This is saying, yeah but stoned astrocytes also don’t inflame anything.
Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine – Yes yes astrocytes shape the synapse, but this type of work is less useful when we aren’t monitoring broader astrocytic signaling. I’m more curious at this point about what amount of data (or even types) goes through the astrocyte direct network vs. the indirect network (via neurons, etc).
Astrocyte signaling and interactions in Multiple Sclerosis – They should rename it to Astrocytes Gone Wild! Bet they’d get a lot more funding.