pyramidal spine-neck EPSPs

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davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

NEURON does seem to be the best neuronal simulator and it's shareable. The shoulders of giants! Ty sir and permit the revision 'play with your own blocks'.
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

I opened ModelDB.science in my browser > entered Chiu into the filter, found Chiu et al Compartmentalization …2013 > Files > Mod folder >
I found 12 mod files, some already in my spine_neck model, some I did not recognize:
ca.mod, ca_a1g.mod, ca_a1h.mod, cad.mod, constant.mod, distr.mod, exp2syncur.mod, exp2synsat.mod, im.mod, kca.mod, km.mod, kv.mod, na.mod, zoidsvn.mod
I resisted the temptation to load them all into my Desktop HOC folder to compile them all with my Terminal. I need to focus on whether or not calcium ion is presently entering the NMDA channel (and to a much lesser extent the AMPA channel), and on whether I need to add a voltage-gated calcium mechanism. I should not need extra potassium, sodium or voltage mechanisms.
The goal is a graph of calcium ion influx into the sensory spine-neck in response to glutamatergic transmission.
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

Soledad Miranda-Rottman PhD, an author and team member, has sent me the Tazerart et al 2022 reprint and will visit the Forum. Ty Soledad.
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

I asked Bard, “In my NEURON program simulation of a pyramidal neuron spine neck calcium ion concentration, which mechanisms are needed in the segment?”
Bard responded:
// Define the spine neck.
spine_neck = compartment(name='spine_neck', length=100.0, diameter=10.0)
// Define the membrane.
spine_neck.membrane = h.memb(name='spine_neck_membrane')
// Add a voltage-gated calcium channel to the membrane.
spine_neck.membrane.add_channel('hh')
// Add a ligand-gated calcium channel to the membrane.
spine_neck.membrane.add_channel('nmda')
// Add a passive diffusion mechanism for Ca2+ across the membrane.
spine_neck.membrane.add_passive('ca')
// Define the cytoplasm.
spine_neck.cytoplasm = h.cytoplasm(name='spine_neck_cytoplasm')
// Add a calcium binding protein to the cytoplasm.
spine_neck.cytoplasm.add_protein('calmodulin')
// Add a calcium-dependent enzyme to the cytoplasm.
spine_neck.cytoplasm.add_enzyme('calcium_dependent_kinase')
// Run the simulation.
h.run()
// Plot the calcium ion concentration in the spine neck.
h.plot(spine_neck.ca)
Use code with caution. This is just a simple example, and you will need to modify it to fit your specific needs. For more information on how to create NEURON models, please refer to the NEURON documentation.
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

I asked BARD* again:
Prompt: In response to a 16 ms visual stimulus, what will be the duration of visual cortex pyramidal spine neck calcium influx.
BARD* Response: The duration of visual cortex pyramidal spine neck calcium influx in response to a 16 ms visual stimulus is approximately 100 ms. This is based on the research of Maffezzoli et al. (1981), who found that calcium influx into pyramidal spine necks in the visual cortex peaks at around 100 ms after a visual stimulus. The calcium influx is thought to be important for the initiation of long-term potentiation (LTP), a form of synaptic plasticity that is thought to underlie learning and memory.
Prompt: What is the full reference for Maffezzoli et al. (1981):
BARD* Response: Maffezzoli, G., Liano, G., & Maffei, L. (1981). Calcium influx into pyramidal spine necks in the visual cortex of the rat. Brain Research, 206(1), 17-28.

Google Scholar: Your search - did not match any articles.
ted
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Re: pyramidal spine-neck EPSPs

Post by ted »

Sorry for the long lapse, but things have been unusually busy here for the past few weeks.

A 1981 reference is pretty ancient; experimental methods have improved considerably since then. However, it's a good starting point. See if you can find a publication that cited it, reports relevant experimental results, and is (much) more recent.

100 ms is a long time. Do the authors attribute that to slow extrusion of Ca (e.g. by pump or Na-Ca exchange)? Nowadays one would have to ask whether that duration is partly due to Ca- or IP3-triggered Ca release from internal stores (smooth endoplasic reticulum), but in the early 1980s nobody knew that SER existed in dendrites or spines (or anywhere else in a neuron, for that matter).
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

Thank you Professor.
That 1981 reference was an “hallucination” by BARD AI. No such reference exists, although I believe the 100 ms spine-neck duration is correct.

I have written to the Montreal lab again asking if they could look at the following list of NEURON hoc file commands and see if their model is different.

https://docs.google.com/document/d/1VHS ... sp=sharing

I’m not getting any calcium concentration increase in the spine-neck in response to a volley of synaptic transmissions.
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

Jean-marie Bouteiller at USC has also agreed to help me figure out why I can't get a decent calcium flow into sensory spine-necks.
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

We have the best modeling minds at Yale, U Montreal and USC but no calcium influx into sensory spine-necks.
I suspect that in addition to AMPA, NMDA, and VGCC model processes, there may also need to be a 5HT-2A receptor process that indirectly increases calcium influx near but not in the postsynaptic density. On a more fundamental level, we know that the EPSP from the synaptic spine-head passes through the spine to the dendrite and soma in about 5 ms, while the spine neck ca++ influx continues for 30 to 100 ms. This may simply be a matter of a sufficient number of synaptic glutamatergic transmissions, but there are other possibilities such as adding VGCCs to the spine-neck as well as the spine-head.
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

I have not added a GABA receptor on the spine-head or neck because I believe they are found only on the pre-synaptic side of the synaptic cleft. Ted may disagree; I cite his 2013 paper (Chiu, C. Q., Lur, G., Morse, T. M., Carnevale, N. T., Ellis-Davies, G. C., & Higley, M. J. (2013). Compartmentalization of GABAergic inhibition by dendritic spines. Science, 340(6133), 759-762). Also, I am modeling sensory spines synapsed from the thalamus, not hippocampal spines synapsed from adjacent cortex nor prefrontal spines which are not sensory.
davidhubbardmd
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Re: pyramidal spine-neck EPSPs

Post by davidhubbardmd »

Jui-Yun Chang, PhD and her colleagues at Duke have studied calmodulin (CaM) and proposed a model in their 2019 paper: Chang, J. Y., Nakahata, Y., Hayano, Y., & Yasuda, R. (2019). Mechanisms of Ca2+/calmodulin-dependent kinase II activation in single dendritic spines. Nature communications, 10(1), 2784. I have reached out to Dr. Chang but in the meantime I note that she’s shown that a brief pulse of glutamate uncaging induces a Ca2+ transient elevation that lasts 100 ms in the stimulated spine. This in turn activates CaMKII𝝰 peaking in about 500 ms and decaying over 10 seconds. The fraction of CaMKII𝝰 bound to Ca2+/CaM remains constant during repetitive uncaging pulses with a transient binding tau of about 1 second.
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