Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Interneuron Types in Distinct Behavior


Nature 498, 363–366 (20 June 2013)

Distinct behavioural and network correlates of two interneuron types in prefrontal cortex

Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA

D. Kvitsiani, S. Ranade, B. Hangya, H. Taniguchi, J. Z. Huang & A. Kepecs

Max Planck Florida Institute for Neuroscience, One Max Planck Way, Jupiter, Florida 33458-2906, USA.

H. Taniguchi


Neurons in the prefrontal cortex exhibit diverse behavioural correlates, an observation that has been attributed to cell-type diversity. To link identified neuron types with network and behavioural functions, we recorded from the two largest genetically defined inhibitory interneuron classes, the perisomatically targeting parvalbumin (PV) and the dendritically targeting somatostatin (SOM) neurons in anterior cingulate cortex of mice performing a reward foraging task. Here we show that PV and a subtype of SOM neurons form functionally homogeneous populations showing a double dissociation between both their inhibitory effects and behavioural correlates. Out of several events pertaining to behaviour, a subtype of SOM neurons selectively responded at reward approach, whereas PV neurons responded at reward leaving and encoded preceding stay duration. These behavioural correlates of PV and SOM neurons defined a behavioural epoch and a decision variable important for foraging (whether to stay or to leave), a crucial function attributed to the anterior cingulate cortex. Furthermore, PV neurons could fire in millisecond synchrony, exerting fast and powerful inhibition on principal cell firing, whereas the inhibitory effect of SOM neurons on firing output was weak and more variable, consistent with the idea that they respectively control the outputs of, and inputs to, principal neurons. These results suggest a connection between the circuit-level function of different interneuron types in regulating the flow of information and the behavioural functions served by the cortical circuits. Moreover, these observations bolster the hope that functional response diversity during behaviour can in part be explained by cell-type diversity.

To investigate whether distinct interneuron types can encode specific behavioural variables we recorded the activity of inhibitory neurons expressing parvalbumin and somatostatin markers. PV basket cells are thought to control the spiking output of pyramidal neurons, whereas most SOM interneurons, known as Martinotti cells target distal dendrites, gating the inputs arriving onto pyramidal cells. To target these interneuron types for recordings, we used PV-Cre and SOM-Cre driver mouse lines in combination with adeno-associated viruses to deliver channelrhodopsin-2 (ChR2), rendering neurons light sensitive. Miniature microdrives housing 6 movable tetrodes and an optical fibre were implanted in deep layers of the anterior cingulate cortex (ACC). We recorded well-isolated single units (n = 1,339 from 6 PV-Cre and 6 SOM-Cre mice) and delivered brief pulses (1ms) of blue light to elicit short-latency action potentials in ChR2-expressing neurons that served as a physiologic tag24. To identify directly light-activated units we developed an optical-tagging test based on a statistical measure that yields a P value testing whether light-activation induced significant changes in spike timing. Significantly activated units (P<0.01) showed similar spontaneous and light evoked waveforms (correlation coefficient, r>0.85), low-latency light-induced response (<4ms), and low first-spike jitter signatures of direct light-activation.

Optogenetic identification of many individual interneurons, in combination with simultaneous recording from a large number of their neighbours, allowed us to investigate the physiological impact of different inhibitory subtypes during behavioural epochs without light stimulation. To identify possible functional connectivity between neurons, we computed cross-correlograms (CCGs)—counts of spike co-occurrences in the putative pre- and postsynaptic neuron pairs at different time lags. Significant short-latency interactions were rare among pairs of unidentified ACC neurons.

These results demonstrate that the PV population is capable of millisecond synchronization with fast and precise inhibitory effect on local neural activity.

In contrast to PV pairs, we found no short-timescale correlations between SOM pairs.

The weak observable effect of SOM neurons on the firing output of their neighbours could be due to dendritic inhibition generating input suppression, which is expected to be more difficult to detect using a cross-correlation approach. Thus, PV and SOM interneurons form distinct inhibitory networks: a fast, synchronous PV network generating strong, transient inhibition and an asynchronous SOM network with weaker effect on firing output.

Our findings demonstrate that two major classes of interneurons not only provide distinct modes of inhibition but also display unique behavioural correlates, with temporal and functional specificity comparable to principal neurons. Out of the many behavioural events in the task, the homogeneous responses of PV and NS-SOM interneurons bracketed a defined epoch: from reward approach to leaving, and represented a specific behavioural variable, staying time at the reward zone, critical for foraging decisions, a central function attributed to ACC. How can this temporal and behavioural specificity be understood in the context of our current knowledge of interneurons? First, tuning specificity may arise from the dense, convergent local input these interneuron types receive, enabling them to ‘summarize’ local neural activity, which may be particularly high at the moments when a region is engaged in a task. Second, PV interneurons have been implicated in controlling pyramidal cell output, consistent with the synchronous firing and strong inhibitory coupling we observed. In contrast, SOM neurons are thought to gate long-range inputs to principal cells, and their asynchronous activation and weaker inhibitory impact on firing output is consistent with this role. In our behaviour, input and output regulation might be expected around the foraging decision, consistent with the observed suppression of NS-SOM interneurons during approach followed by the activation of PV interneurons at reward exit. Taken together, our findings suggest a conceptual model in which these interneuron subtypes specialize in temporally regulating the flow of information in a given cortical circuit during the behavioural events relevant to that area. In summary, these observations bolster the long-held hope that probing identified cell-types will reveal the intrinsic logic of cortical circuits under more natural behavioural settings.

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