Functional diversity of somatostatin interneurons in visual cortical circuits

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

First Advisor

Cardin, Jess

Abstract

A diverse set of GABAergic interneurons promote flexibility in neocortical operations such as visual processing. One class of interneurons, dendrite-targeting interneurons that co-express the peptide Somatostatin (SST-IN), play critical roles in behavioral state-dependent modulation and sensory processing. In the superficial layers of primary visual cortex, SST-INs show increased excitatory drive during locomotion in both spontaneous and visually evoked activity and larger receptive field sizes. Because of their sensitivity to large stimuli, they are thought to mediate surround suppression in neighboring excitatory cells. However, SST-INs comprise a series of molecularly distinct subpopulations, particularly in deep cortical layers, and it remains unknown whether their functional properties are similarly diverse. To investigate the functional diversity of SST-INs, we performed 2-photon calcium imaging using a red-shifted calcium indicator that allows for greater tissue depth-penetration. This technical approach allowed us to image SST-INs across the first five layers of primary visual cortex (V1). We found no differences in state modulation of spontaneous activity across SST-INs in different cortical layers. However, unlike primary somatosensory cortex, we found heterogeneity in the state-dependent modulation of visually evoked activity of SST-INs across layers. Layer 5 SST-INs exhibit less modulation with locomotion than SST-INs in superficial or granular layers. We further explored SST-IN responses to different types of contextual visual stimuli. We found SST-INs to be more positively modulated by orthogonal surround stimuli in layer 5 than in layers 2/3 and 4. This was especially prominent during locomotion, where layer 2/3 SST-INs exhibit more negative modulation and layer 5 SST-INs more positive modulation. These differences in functional properties suggest distinct roles for SST-INs in different layers in regulating local excitatory pyramidal neuron activity. To better understand the role of subtype heterogeneity, we recorded from Chrna2- and HPSE-expressing SST-INs, two key subpopulations of SST-INs that occur in layer 5. Whereas the HPSE cells exhibit similar functional properties to those of the overall layer 5 SST-IN population, Chrna2 cells showed modest receptive field sizes, markedly stronger surround suppression, and a lack of contextual modulation. Overall, these findings highlight functional diversity within the SST-IN population and suggest that molecularly distinct subpopulations may play discrete roles in regulating circuit function. Our data provide a critical first step towards understanding the importance of inhibitory interneuron diversity and laminar differences in canonical cortical circuit motifs across layers.

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