The role of AMPA receptor calcium permeability in hippocampal interneuron plasticity, circuit (360G-Wellcome-105411_Z_14_A)

£43,169

Calcium-permeable AMPA receptors (CP-AMPARs), largely absent from principal cells in adulthood, are highly expressed in several interneuron populations, including hippocampal parvalbumin-positive basket cells (PVBCs). The contribution of CP-AMPARs to PVBC activity, plasticity and subsequently network functions is of great interest, given the role of these cells in hippocampal gamma oscillatory activity, implicated in information maintenance during working memory. However, the contribution of PVBC CP-AMPARs to network dynamics central to gamma oscillation generation, and consequentially effective working memory, hasn’t been established. We aim to look at multiple levels to ascertain the impact of CP-AMPAR manipulations on neural and behavioural function. First, we plan to characterize the effects of CP-AMPAR blocker philanthotoxin-433 on network dynamics and spatial memory. Second, we will selectively delete GluR1 in PV+ cells, resulting in constitutive loss of the primary CPAMPAR contributing subunit, and establish the impact of CP-AMPAR loss at each level. Finally, given that CP-AMPARs are defined by their lack of GluR2 subunit, and that PVBCs do not express GluR2, we aim to artificially overexpress GluR2 in PVBCs using an adenoviral agent in order to remove AMPAR calcium permeability without decreasing overall cellular AMPAR levels, and subsequently fully characterize the impact of this permeable-to-impermeable AMPAR switch.

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Grant Details

Amount Awarded 43169
Applicant Surname Cooper
Approval Committee Internal Decision Panel for C&S
Award Date 2016-09-30T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title PhD Studentship (Basic)
Internal ID 105411/Z/14/A
Lead Applicant Mr Matthew Cooper
Partnership Value 43169
Planned Dates: End Date 2018-09-30T00:00:00+00:00
Planned Dates: Start Date 2015-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Stephen Tucker