The Nucleus Accumbens as a Switchboard: Heterosynaptic Suppression in the Ventral Striatum

Abstract

Many brain circuits control behavior through the integration of information provided by separate inputs onto a common target neuron. Medium spiny neurons (MSNs) in the ventral striatum (VS) receive converging excitatory afferents from the prefrontal cortex (PFC), hippocampus (HP), and thalamus, among others, and the integration of these inputs is critical for shaping goal-directed behaviors. Although under baseline conditions the membrane activity of MSNs is controlled largely by the HP, the PFC can elicit up states in MSNs during periods of high frequency activity, such as that which occurs during decision making epochs. Moreover, during epochs of high PFC activity, the VS loses synchrony with the HP. It is therefore possible that PFC inputs locally attenuate responses to other glutamatergic inputs to the VS. We investigated whether strong, transient PFC activation can disengage the VS from the HP by measuring the effect of high frequency PFC stimulation on MSN responses to stimulation of other synaptic inputs. Using in vivo intracellular recordings, we found that delivering trains of stimuli to the PFC suppresses HP- and thalamus-evoked synaptic responses in the VS, partially through a GABAergic mediator. These findings indicate that high frequency PFC activity overrides HP control of MSN up state transitions, and provide evidence of heterosynaptic inhibition in this system in vivo. This interaction may enable the PFC to exert influence on basal ganglia loops during decision-making instances with minimal disturbance from ongoing contextual inputs.