Abstract
BackgroundCo-morbidity of schizophrenia and drug use has been attribute to common pathophysiology of mesocortical circuit. We modeled a behavioral disruption to this circuit in rodents by using a task where actions were consistently rewarded but probabilistically punished. Our data reveal dynamic coding schemes of the VTA-mPFC neural circuit in representing risk of punishment and punishment-based modulation of rewarded actions.MethodsSpike activity and local field potentials were recorded during simultaneously from ventral tegmental area and medial prefrontal cortex (PFC), two reciprocally connected mesocortical regions, in rodents as they performed a task where actions were consistently rewarded but probabilistically punished. This model allowed us to reveal dynamic coding schemes of the VTA-mPFC neural circuit in representing risk of punishment and punishment-based modulation of rewarded actions.ResultsAt the single unit level (n=167 mPFC n=102 VTA units), we found that ensembles of VTA and mPFC neurons encode the contingency between action and punishment. At the network level, we found that coherent theta oscillations synchronize the VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment contingencyDiscussionDuring reward-seeking actions, risk of an aversive outcome and anxiety disrupts dopamine neuron-driven synchrony between PFC and VTA
Highlights
Recent work with a dopamine 2 receptor (D2R) over-expressing (D2R-OE) mouse has suggested that this receptor over-expression leads to a highly plastic increase in bridging collaterals from the associative striatum (AST) to the external segment of the globus pallidus (GPe)
Because of the densely interconnected nature of basal ganglia-thalamo-cortical signaling circuitry, we hypothesized and demonstrated in a recent publication that the resting state functional connectivity (RSFC) of AST to multiple cortical and thalamic subregions is broadly disrupted in unmedicated patients with schizophrenia
Recent work with a 22q11 deletion mouse, which models a similar syndrome in humans that is strongly associated with schizophrenia, has shown that these mice exhibit a D2R-mediated reduction in the strength of excitatory post-synaptic potentials in primary auditory cortex in response to stimulation of the medial geniculate nucleus (MGN) of the thalamus
Summary
Co-morbidity of schizophrenia and drug use has been attribute to common pathophysiology of mesocortical circuit. Methods: Spike activity and local field potentials were recorded during simultaneously from ventral tegmental area and medial prefrontal cortex (PFC), two reciprocally connected mesocortical regions, in rodents as they performed a task where actions were consistently rewarded but probabilistically punished This model allowed us to reveal dynamic coding schemes of the VTA-mPFC neural circuit in representing risk of punishment and punishment-based modulation of rewarded actions. We found that coherent theta oscillations synchronize the VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions This synchrony declined as a function of punishment contingency Discussion: During reward-seeking actions, risk of an aversive outcome and anxiety disrupts dopamine neuron-driven synchrony between PFC and VTA. 27.4 STRUCTURAL, FUNCTIONAL, AND BEHAVIORAL INSIGHTS OF DOPAMINE DYSFUNCTION REVEALED BY A DELETION IN SLC6A3
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