NEURON TYPE- AND SYNAPSE-SPECIFIC DEFINITION OF DORSAL STRIATAL CIRCUITS RELEVANT TO IMPAIRED GOAL-DIRECTED VERSUS HABITUAL BEHAVIOURS IN MICROBIOTA-DEFICIENT MICE

Coordinated transitions between goal-directed versus habitual behaviours are essential for action selection and are supported in the brain by neuronal representations formed in the dorsal striatum and related structures. The gut microbiota can influence the brain and modify complex behaviours through interactions reported via distinct signalling streams commonly defined as the gut-brain axis. Perturbations to the composition of the gut microbiota, such as in germ-free mice which are deprived of their microbiome from birth, impact on the brain leading to a wide range of behavioural deficits including impaired goal-directed and habitual behaviours. However, the underlying central nervous system pathways and neuronal mechanisms mediating the effects remain to be established. We hypothesise that the influence of the gut microbiota on dorsal striatal neuronal dynamics is mediated via specialised neuron types and synaptic connections susceptible to central nervous system mediators of gut-brain signalling. We are developing a novel quantitative circuit-mapping framework by combining computational analysis, molecular profiling including multi-channel immunohistochemistry, high-resolution confocal microscopy and semi-automated anatomical quantification. Here, we contrasted dorsal striatal neuronal circuits including behaviourally relevant prefrontal cortical afferents in germ-free and conventional mice of both sexes. Using this quantitative mapping, we are defining microbial-status dependent (i) GABAergic and cholinergic neuron types; (ii) their rostro-caudal spatial distributions within striatum; and (iii) synaptic input and axonal innervation patterns. Our results show initial evidence of key biological organisational principles relevant to the understanding of the gut microbiota’s influence on neuronal circuits involved in the coordination of goal-directed versus habitual transitions.