Poster abstracts
Poster number 90 submitted by Meretta Hanson
Satb2 expression in CA1 hippocampal pyramidal cells is necessary for the development of feedforward inhibitory circuits
Meretta A. Hanson (Neuroscience Graduate Program), Priya Nagarajan, Noor Bibi, Alireza Safa (Department of Neuroscience, Ohio State University College of Medicine), Aidan C. Johantges (Neuroscience Undergraduate Program), Alec H. Marshall (Department of Neuroscience, Ohio State University College of Medicine), Jason C. Wester (Department of Neuroscience, Ohio State University College of Medicine)
Abstract:
Pyramidal cells (PCs) in CA1 hippocampus can be parsed based on their radial position as deep and superficial. Previous work found that parvalbumin-expressing basket cells (PVBCs) provide stronger inhibition to deep PCs, which results in greater feedforward inhibition of afferent input from CA3 Schaffer collaterals. Here, we show that the transcriptional regulator Satb2 is necessary for PC differentiation and development, which in turn guides PVBC radial migration and axon targeting. Using mice, we conditionally knocked out (cKO) both copies of Satb2 from only excitatory PCs. We found that the intrinsic membrane properties of superficial PCs changed to resemble those observed in deep PCs. Strikingly, PVBC radial migration and axon targeting was also disrupted, resulting in ectopic localization of both cells and their axons. These changes correlated with ectopic PC expression of CXCL12, a protein that guides PVBC migration and axon targeting. Thus, Satb2 is necessary to sequester CXCL12 to the soma of excitatory PCs. Next, we used paired whole-cell recordings to study synaptic connections between PCs and PVBCs. In control mice, we replicated previous findings that inhibitory postsynaptic currents are larger in deep than superficial PCs. Strikingly, in Satb2 cKO mice, inhibitory currents in superficial PCs increased to match those in deep PCs, while deep PCs remained unchanged relative to control. Finally, we investigated the impact of Satb2 cKO on feedforward inhibition of afferent CA3 Schaffer collateral input to CA1 PCs. We recorded the responses of deep and superficial PCs to CA3 Schaffer collateral stimulation in the presence and absence of GABA blockers. We found that the strength of excitatory afferents is unchanged in Satb2 cKO mice, but feedforward inhibition is selectively enhanced onto superficial PCs. We conclude that Satb2 expression in superficial PCs maintains differential feedforward inhibitory circuitry between deep and superficial layers in CA1, and therefore controls the differential gating of information from CA3 through these two CA1 sublamina.
Keywords: Neural Circuits, Electrophysiology, Hippocampus