Talk abstracts

Talk on Tuesday 03:45-04:00pm submitted by Meretta Hanson

The transcription factor Satb2 regulates pyramidal neuron integration into hippocampal circuits

Meretta A. Hanson (Neuroscience Graduate Program), Devipriyanka Nagarajan (Department of Neuroscience, Ohio State University College of Medicine), 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:
The CA1 region of the hippocampus contains pyramidal cells (PCs) that provide the output of hippocampal learning and memory computations to the rest of the brain. These CA1 PCs are heterogeneous and can be parsed based on laminar position into two subgroups: deep and superficial. Deep and superficial PCs are hypothesized to participate in different aspects of learning and memory due to their differential integration into hippocampal circuitry. For example, parvalbumin-expressing (PV+) basket cells preferentially inhibit deep PCs. This biased inhibition suppresses the output of deep PCs relative to superficial PCs in response to excitatory afferent input from neighboring hippocampal CA3. The mechanisms regulating the development of these different feedforward inhibitory circuits are unknown. Here, we test the hypothesis that the transcription factor Satb2 is critical for proper circuit integration of CA1 PCs. Satb2 is necessary for the differentiation of neocortical pyramidal cell types and is preferentially expressed in superficial PCs of the hippocampus. Using transgenic strategies in mice, we conditionally knocked out (cKO) Satb2 from pyramidal cells during early development. We then performed whole cell patch clamp recordings in acute hippocampal slices to examine the impact of Satb2 loss on PC integration into hippocampal circuits. We found that loss of Satb2 abolishes biased input from PV+ basket cells to deep PCs by preferentially increasing PV+ inhibition of superficial PCs. This increase in feedforward inhibition equalizes the responses of deep and superficial PCs to input from CA3. Thus, Satb2 is necessary for the proper differentiation of superficial PCs to maintain separate computations within CA1.

Keywords: Neural Circuits, Electrophysiology, Hippocampus