Title: Contribution of distinct types of GABAergic interneuron to working memory and decision making
Abstract
The distributed temporal activity in neuronal circuits of the prefrontal cortex combines emotional information with episodic and spatial memory to guide behavioural action. Single neurons of often unknown identity have been shown to exhibit specific firing patterns during spatial navigation and decision-making tasks. The cerebral cortex consists of highly diverse neuronal types with distinct synaptic connectivity, molecular expression profile and contribution to network activity. Neurons can be divided into excitatory pyramidal cells, which use glutamate as a neurotransmitter and give both local and long-range axonal projections, and inhibitory interneurons, which are GABAergic and control the activity and timing of pyramidal cells mainly through local axons. These neurons can be further subdivided on the basis of their distinct axo-dendritic arborisations, subcellular post-synaptic targets, and by their differential expression of signalling molecules, including receptors, ion channels, neuropeptides, transcription factors and Ca2+ binding proteins. We aim to determine how distinct types of neuron support the executive functions of the prefrontal cortex.
We have recorded from identified GABAergic interneurons and pyramidal cells in the prefrontal cortex of freely-moving rats using the juxtacellular recording and labelling technique. We investigated their contribution to network oscillations and a delayed cue-matching-to-place task involving working memory and decision making. The neuronal identity was determined with post-hoc histochemical analysis.
We observed two groups of pyramidal neurons which showed task-related firing patterns: neurons that represented the future goal and neurons that fired preferentially during distinct periods of the task. These firing patterns were modulated by the activity of distinct types of interneuron. For example, we observed that the firing of parvalbumin-expressing basket cells displayed strong modulation according to the task episode. Interestingly, different parvalbumin-expressing basket cells fired preferentially at different episodes during the task (e.g. stimulus, delay, execution). A difference in the firing of parvalbumin-expressing basket cells according to the decisions was observed often only after its execution and during or shortly after reward consumption. Thus, parvalbumin-expressing basket cells support the encoding of temporal sequences and distinct task episodes during working memory and decision making.
We have developed a novel technique that allows the recording of unequivocally identified neurons and show how distinct types of neuron contribute to prefrontal network operations and executive behavior. Our results indicate that GABAergic interneurons release GABA at distinct times to different domains of pyramidal cells contributing to the formation of cell assemblies and representations in the prefrontal cortex.