UC San Diego

The central nervous system is a crystalline-like structure which is constructed through the repeated assembly of stereotyped circuits. These circuits connect a relatively homogenous population of excitatory principal cells with a diverse population of inhibitory interneurons. One of the most striking features of the diversity of the interneurons is the specificity of their axonal arborizations. Each class of interneuron targets a specific subcellular compartment; for instance, different populations of interneurons mediate somatic and dendritic inhibition. However, in order to fully appreciate the implications of having different compartments under discrete inhibitory control we must know three things about each class of interneuron: its impact on the postsynaptic cell, the patterns of activity through which it is recruited, and its regulation by neuromodulators. We argue that these three properties will allow us to define the role of an inhibitory interneuron in the circuit. In order to investigate the roles of the diverse population of interneurons, we made intracellular recordings from identified interneurons in slices of the rat hippocampus. Through paired intracellular and extracellular recordings, we found that GABA release from both somatic and dendritic targeting interneurons results in the hyperpolarization of pyramidal cells. Within the groups of somatic and dendritic targeting interneurons there was additional diversity in their intrinsic properties, patterns of excitation, and modulation. By dividing the interneurons according to both the location of their axonal arborization (i.e. somatic or dendritic) and their intrinsic firing patterns (i.e. regular and fast spiking), we were able to define four relatively homogenous populations with distinct patterns of recruitment and impacts on their targets. In addition we found that neuromodulators could independently suppress the different classes of interneurons, suggesting that the network can actively regulate the timing and strength of inhibition. This work provides evidence for the precise roles of somatic and dendritically targeting interneurons in coordinating network activity. In addition, it proposes a methodology for understanding the role of the diverse population of inhibitory interneurons in the intact cortical circuit