Neuronal SNAP-23 scales hippocampal synaptic plasticity and memory

Huang, M.; Bin, N.-R.; Rai, J.; Ma, K.; Chow, C. H.; Eide, S.; Harada, H.; Xiao, J.; Feng, D.; Sun, H.-S.; Feng, Z.-P.; Gaisano, H. Y.; Pessin, J.; Monnier, P. P.; Okamoto, K.; Zhang, L.; Sugita, S.

doi:10.1101/2022.08.04.502541

bioRxiv · 10.1101/2022.08.04.502541

Neuronal SNAP-23 scales hippocampal synaptic plasticity and memory

Huang, M.·Bin, N.-R.·Rai, J.·Ma, K.·Chow, C. H.·Eide, S.·Harada, H.·Xiao, J.·Feng, D.·Sun, H.-S.·Feng, Z.-P.·Gaisano, H. Y.·Pessin, J.·Monnier, P. P.·Okamoto, K.·Zhang, L.·Sugita, S.

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Abstract

Soluble NSF Attachment protein REceptor (SNARE)-mediated membrane fusion plays a crucial role not only in presynaptic vesicle exocytosis but also in postsynaptic receptor delivery. The latter is considered particularly important for long-term synaptic plasticity and learning and memory, yet underlying mechanisms including the identity of the key SNARE proteins remain elusive. Here, we investigate the role of neuronal Synaptosomal-Associated Protein-23 (SNAP-23) by analyzing pyramidal-neuron specific SNAP-23 conditional knockout (cKO) mice. SNAP-23 immunostaining in postsynaptic spines was effectively decreased in the SNAP-23 cKO hippocampus. Electrophysiological analysis of SNAP-23 deficient neurons using acute hippocampal slices showed normal basal neurotransmission in CA3-CA1 synapses with unchanged AMPA and NMDA currents. Nevertheless, we found theta-burst stimulation induced long-term potentiation (LTP) was vastly diminished in SNAP-23 cKO. Moreover, unlike syntaxin-4 cKO mice in which both basal neurotransmission and LTP decrease manifested changes in a broad set of behavioral tasks, deficits of SNAP-23 cKO is more limited to spatial memory. Our data reveal that neuronal SNAP-23 is selectively crucial for synaptic plasticity and spatial memory without affecting basal glutamate receptor function.

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Huang, M., Bin, N.-R., Rai, J., Ma, K., Chow, C. H., Eide, S., Harada, H., Xiao, J., Feng, D., Sun, H.-S., Feng, Z.-P., Gaisano, H. Y., Pessin, J., Monnier, P. P., Okamoto, K., Zhang, L., Sugita, S.. 2022-08-06. Neuronal SNAP-23 scales hippocampal synaptic plasticity and memory. https://doi.org/10.1101/2022.08.04.502541

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