Cytosolic PSD-95 interactor alters functional organization of neural circuits and AMPA receptor signaling independent of PSD-95 binding

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Abstract
  • Cytosolic PSD-95 interactor (cypin) regulates many aspects of neuronal development and function, ranging from dendritogenesis to synaptic protein localization. While it is known that removal of postsynaptic density protein-95 (PSD-95) from the postsynaptic density decreases synaptic N-methyl-D-aspartate (NMDA) receptors and that cypin overexpression protects neurons from NMDA-induced toxicity, little is known about cypin’s role in AMPA receptor clustering and function. Experimental work shows that cypin overexpression decreases PSD-95 levels in synaptosomes and the PSD, decreases PSD-95 clusters/μm2, and increases mEPSC frequency. Analysis of microelectrode array (MEA) data demonstrates that cypin or cypinΔPDZ overexpression increases sensitivity to CNQX (cyanquixaline) and AMPA receptor-mediated decreases in spike waveform properties. Network-level analysis of MEA data reveals that cypinΔPDZ overexpression causes networks to be resilient to CNQX-induced changes in local efficiency. Incorporating these findings into a computational model of a neural circuit demonstrates a role for AMPA receptors in cypin-promoted changes to networks and shows that cypin increases firing rate while changing network functional organization, suggesting cypin overexpression facilitates information relay but modifies how information is encoded among brain regions. Our data show that cypin promotes changes to AMPA receptor signaling independent of PSD-95 binding, shaping neural circuits and output to regions beyond the hippocampus.
TitleCytosolic PSD-95 interactor alters functional organization of neural circuits and AMPA receptor signaling independent of PSD-95 binding
CreatorRodriguez, A. R.
Kwon, M.
O'Neill, K. M.
Firestein, B. L.
Vigilante, N. F.
McEwan, P. P.
Meaney, D. F.
Akum, B. F.
Anderson, E. D.
Stawicki, Tamara M.
PublisherNetwork Neuroscience
Academic DepartmentNeuroscience
DivisionNatural Sciences
Date Issued2021
Date Available2021-02-19
TypeArticle
LanguageEnglish
KeywordCypin
AMPA receptors
Microelectrode array
Electrophysiology
Hippocampal neurons
Neural circuits
Bibliographic CitationRodriguez, A. R., et al (2021). "Cytosolic PSD-95 interactor alters functional organization of neural circuits and AMPA receptor signaling independent of PSD-95 binding." Network Neuroscience 5 (1): 166-197.
Standard IdentifierHandle 10385/v405sb70j
DOI 10.1162/netn_a_00173
Permalinkhttp://hdl.handle.net/10385/v405sb70j
Rights Statement Creative Commons - Attribution Creative Commons - Attribution
Rights HoldersMassachusetts Institute of Technology
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