Behavioral consequences of GABAergic neuronal diversity

https://doi.org/10.1016/j.conb.2013.11.002Get rights and content

Highlights

  • Hippocampal CA1 PV+ INs regulate PC spike timing and working memory.

  • Photoactivation of V1 PV+ INs increases orientation discrimination.

  • Disinhibition in auditory cortex is linked to fear learning and reinforcement.

  • Role of dendritic inhibition may be attenuated under anesthesia.

The majority of cellular diversity in the hippocampus and neocortex derives from a relatively small population of local inhibitory interneurons. Recent technological advances have facilitated the recording and manipulation of defined inhibitory cell classes in awake rodents, revealing new and surprising roles for these cells in local circuit function and behavior. Here we review recent progress in the analysis of inhibitory interneuron subtypes in neocortex and hippocampus during behavior, and suggest opportunities and considerations for extending this research program.

Section snippets

Hippocampus

The composition of inhibitory interneurons in neural networks has been most extensively studied in hippocampal area CA1 – considered to be an architecturally simplified cortical circuit. One approach to strictly define cell classes without genetic tools is to label recorded interneurons with dyes, then stain for proteins expressed by the recorded cell. This technique has been used in freely-moving rats to show the firing of soma-targeting basket cells is more sensitive to behavioral state than

The influence of disinhibition

Although these novel techniques give the experimenter unparalleled access to distinct cell types (eg. PV+ interneurons), this must not be mistaken for access to specific synapses (eg. PV-to-PC connections). Interneurons are densely interconnected, both between and within types (Figure 2a,b); such disinhibition may have important consequences for interpreting the effects of manipulating specific cell types [46].

For instance, subpopulations of PV+ soma-targeting and SOM+ dendrite-targeting

Considerations for studying dendritic inhibition

Dendrites can perform supra-linear synaptic integration under certain conditions [59], which can disproportionately influence PC output by driving burst spikes [60]. Consequently, the effects of manipulating dendritic inhibition are highly sensitive to the state of the animal. Dendritic activity in PCs is greatly reduced in anesthetized animals [61] and even in awake animals not actively engaged in a task [42•, 62], suggesting PCs will be driven by synaptic integration at the soma/axon initial

Future directions

The pioneering studies reviewed here are a first step towards understanding the functional roles of inhibitory interneurons in behaviors dependent on the hippocampus and neocortex. To move forwards, investigators must be able to read-out the activity of defined interneurons during behavior, and then selectively perturb this activity during the behaviour – ideally while recording from PCs. By performing complementary experiments in multiple interneuron types, investigators can narrowly define

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

M.L.-B. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Postgraduate Scholarship. A.L. is supported by the Searle, McKnight and Human Frontiers Science Program Grants.

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