3 ms·

The spacial characteristic is important because activity at two nearby dendrites receiving excitatory (or inhibitory) inputs have an additive effect which is gr

The spacial characteristic is important because activity at two nearby dendrites receiving excitatory (or inhibitory) inputs have an additive effect which is greater the closer they are, this is because the signal is based on concentration of ions and when those signals are closer together they can surpass the concentration threshold that's needed to trigger voltage gated ion channels to open.

bubblyworld 2y ago
Interesting, thanks for the basics. That makes sense - I'm a bit confused about how inhibition vs excitation works if they're both based on ion concentration (is it like positive vs negative ions, or a different mechanism entirely?), but I'll do some googling!
- alan-hn 2y ago
  Different ions with different charges. Sodium (Na^+) as you can see has one positive charge per ion, as does potassium (K^+), calcium has two (Ca^2+), and hydrogen has one (H^+). This charge is balanced with negative charges, a minority from chloride (Cl^-) and the majority from proteins. When it comes to proteins, they are comprised of amino acids which have varying charges and proteins generally end up with a negative charge from all of the sites where they can be protonated. Just for clarification, protonation is where a H+ (a proton) can ironically bind to a molecule with a negative charge, this is how most acids work (that's a generalization don't @ me, chemists) So we have a shitload of proteins inside the cell with a shitload of negative charges, we have a variety of ions with positive charges, and we have ion channels which are transmembrane proteins that have a specific structure to allow certain ions of one charge or size or just all ions in general to pass through their pore. Some are leak channels which are almost always open, some open when a ligand (other molecule) binds, some open when they sense a certain voltage. That takes us to difference in charge. The cell membrane acts as a capacitor, separating charge. There are many pumps that pump out positive ions to maintain this separation and different cells can sit at different voltages where the voltage is simply the difference in charge between the intracellular and extracellular space, this can be measured in whole cell configuration patch clamp experiments where we attach a pipette with a tip smaller than a cell to the membrane and apply suction to break into the cell so we can get a reading but that's a whole topic on its own When it comes to excitation vs inhibitions, it really is about positive vs negative charges. Excitatory ion channels such as kainate AMPA and NMDA receptors pass cations, the positive ions, while GABAa and glycine receptors are ion channels that selectively allow Cl^- into the cell in adults. The developing brain is weird and backward when it comes to Cl^- so again, another topic
  - bubblyworld 2y ago
    Wild, that's really complicated. A bit of a tangent, but one takeaway for me there is that neural nets are _far_ more dissimilar to brains than I thought. Sounds like a lot more going on than "signals add up to threshold"!
    - alan-hn 2y ago
      Absolutely, the brain is the most complicated system in the universe that we are aware of. Something I usually tell people when making comparisons between modern ANNs and biological brains is that there is more computational complexity in a single neuron than the largest ANN All of this doesn't even go into the variation in proteins. For example, AMPA receptors are ion channels, right? One channel is made up of 4 subunits which each is a single polypeptide protein string folded up. There not only are multiple different subunits that can be swapped out to change the properties of the ion channel such as open time, conductance, and ion selectivity, but the subunits can also have posttranslational modifications such as phosphorylation that also changes these properties (besides selectivity iirc) All of this allows incredible nuance for how this one channel responds to stimulation and add on top of that we get more or less AMPA receptors inserted in the membrane at a synapse. Now multiply all of that nuance times all of the synaptic boutons and other receptor proteins Yet again adding more complexity are g-protein coupled receptors that aren't ion channels but cause other changes that may be longer lasting inside the neuron from impacting genetic expression or modifying epigenetics to impacting other ion channels or their expression and this is barely scratching the surface of overall complexity of one singe cell We have billions of these fuckin things all interconnected in a complex web many having thousands of connections that are continuously being modified, created, and destroyed And there are many more signaling pathways besides synaptic such as volume transmissions where neurotransmitters essentially diffuse away from the release site to hit receptors on the cell bodies of far away neurons, we have neuropeptides that can be released from the same synapse as other transmitters but only under specific conditions that can impact near or far cells, we have glia such as astrocytes and microglia that interact with synapses and help with cleanup, regulation, and of course more signaling
      - 2y ago

bubblyworld 2y ago

Interesting, thanks for the basics. That makes sense - I'm a bit confused about how inhibition vs excitation works if they're both based on ion concentration (is it like positive vs negative ions, or a different mechanism entirely?), but I'll do some googling!

alan-hn 2y ago
Different ions with different charges. Sodium (Na^+) as you can see has one positive charge per ion, as does potassium (K^+), calcium has two (Ca^2+), and hydrogen has one (H^+). This charge is balanced with negative charges, a minority from chloride (Cl^-) and the majority from proteins. When it comes to proteins, they are comprised of amino acids which have varying charges and proteins generally end up with a negative charge from all of the sites where they can be protonated. Just for clarification, protonation is where a H+ (a proton) can ironically bind to a molecule with a negative charge, this is how most acids work (that's a generalization don't @ me, chemists) So we have a shitload of proteins inside the cell with a shitload of negative charges, we have a variety of ions with positive charges, and we have ion channels which are transmembrane proteins that have a specific structure to allow certain ions of one charge or size or just all ions in general to pass through their pore. Some are leak channels which are almost always open, some open when a ligand (other molecule) binds, some open when they sense a certain voltage. That takes us to difference in charge. The cell membrane acts as a capacitor, separating charge. There are many pumps that pump out positive ions to maintain this separation and different cells can sit at different voltages where the voltage is simply the difference in charge between the intracellular and extracellular space, this can be measured in whole cell configuration patch clamp experiments where we attach a pipette with a tip smaller than a cell to the membrane and apply suction to break into the cell so we can get a reading but that's a whole topic on its own When it comes to excitation vs inhibitions, it really is about positive vs negative charges. Excitatory ion channels such as kainate AMPA and NMDA receptors pass cations, the positive ions, while GABAa and glycine receptors are ion channels that selectively allow Cl^- into the cell in adults. The developing brain is weird and backward when it comes to Cl^- so again, another topic
- bubblyworld 2y ago
  Wild, that's really complicated. A bit of a tangent, but one takeaway for me there is that neural nets are _far_ more dissimilar to brains than I thought. Sounds like a lot more going on than "signals add up to threshold"!
  - alan-hn 2y ago
    Absolutely, the brain is the most complicated system in the universe that we are aware of. Something I usually tell people when making comparisons between modern ANNs and biological brains is that there is more computational complexity in a single neuron than the largest ANN All of this doesn't even go into the variation in proteins. For example, AMPA receptors are ion channels, right? One channel is made up of 4 subunits which each is a single polypeptide protein string folded up. There not only are multiple different subunits that can be swapped out to change the properties of the ion channel such as open time, conductance, and ion selectivity, but the subunits can also have posttranslational modifications such as phosphorylation that also changes these properties (besides selectivity iirc) All of this allows incredible nuance for how this one channel responds to stimulation and add on top of that we get more or less AMPA receptors inserted in the membrane at a synapse. Now multiply all of that nuance times all of the synaptic boutons and other receptor proteins Yet again adding more complexity are g-protein coupled receptors that aren't ion channels but cause other changes that may be longer lasting inside the neuron from impacting genetic expression or modifying epigenetics to impacting other ion channels or their expression and this is barely scratching the surface of overall complexity of one singe cell We have billions of these fuckin things all interconnected in a complex web many having thousands of connections that are continuously being modified, created, and destroyed And there are many more signaling pathways besides synaptic such as volume transmissions where neurotransmitters essentially diffuse away from the release site to hit receptors on the cell bodies of far away neurons, we have neuropeptides that can be released from the same synapse as other transmitters but only under specific conditions that can impact near or far cells, we have glia such as astrocytes and microglia that interact with synapses and help with cleanup, regulation, and of course more signaling
    - 2y ago