Distinct roles for inhibitory neuron subtypes in cortical circuits : an examination of their structure, function, and connectivity

Abstract

Parvalbumin-containing (PV+) neurons and somatostatin-containing (SOM+) neurons are two key cortical inhibitory cell classes that are poised to play distinct computational roles in cortical circuits: PV+ neurons form synapses on the perisomatic region near the spike initiation zone of target cells, while SOM+ neurons form synapses on distal dendrites. The goals of this thesis are to better understand the functional roles of these two cell types with four major lines of questioning. 1) When and how do PV+ and SOM+ neurons respond to visual stimuli? 2) How do inhibitory neurons obtain their response selectivity? 3) How do PV+ and SOM+ neurons affect the responses of their targets? and 4) What are the targets of PV+ and SOM+ neurons? We used Cre-lox recombination to introduce either fluorescent protein or channelrhodopsin to PV+ or SOM+ neurons, targeting these cells for two-photon targeted physiological recording and morphological reconstruction, or selectively stimulating the population of PV+ or SOM+ neurons or stimulating single PV+ or SOM+ neurons. We find diverse response properties within both groups, suggesting that further functional subclasses of PV+ and SOM+ neurons may exist. Furthermore, orientation selectivity was strongly correlated to dendritic length in PV+ neurons, whose orientation preferences matched the preferences of neighboring cells, implying that inhibitory neurons may obtain selectivity by spatially limiting their sampling of the local network. When we stimulated PV+ and SOM+ neurons, we found that they perform distinct inhibitory operations on their targets: PV+ neurons divide responses while SOM+ neurons subtract. Even single PV+ and SOM+ neurons were capable of suppressing responses of other cells in the local network, but their functional targeting was sparse and followed different rules of wiring: PV+ neurons functionally suppressed a higher percentage of cells that shared their own tuning, while SOM+ neurons seemed to target other neurons independently of their preferred orientations. By studying the response properties and functional impacts of PV+ and SOM+ neurons in the intact primary visual cortex, we have gained insight into what information these cells are carrying and how they contribute to the response properties of other cells, which apply to cortical circuits in general.