Previous work has shown that damage to the dorsal hippocampus (DH) occurring at recent, but not remote, timepoints following acquisition produces a deficit in trace conditioned fear memory expression. The opposite pattern has been observed with lesions to the medial prefrontal cortex (mPFC). The present studies address: (1) whether these lesion effects are observable within 30 d of training; (2) whether lesions of the ventral hippocampus (VH) produce temporally graded retrograde amnesia similar to DH lesions; and (3) whether the lesion-to-test interval critically contributes to these lesion deficits. In Experiment 1, excitotoxic lesions of the DH, VH, or mPFC were made at 1 or 30 d following trace fear conditioning. DH and VH lesioned animals showed a deficit in freezing to the tone at the recent, but not remote, timepoint. Medial PFC lesioned animals showed the opposite pattern. In Experiment 2, lesions to DH, VH, or mPFC were made 1 d following training, while testing occurred 30 d later. There were no deficits in freezing to the tone in any lesion condition compared to controls. These results suggest that systems consolidation of trace fear memory occurs within 30 d of acquisition, but does not depend on hippocampus -mPFC interactions during this period.

The mouse has emerged as an advantageous species for studying the brain circuitry that underlies complex behavior and for modeling neuropsychiatric disease. The transition from flexible, goal-directed actions to inflexible, habitual responses is argued to be a valid and reliable behavioral model for studying a core aspect of corticostriatal systems that is implicated in certain forms of psychopathology. This transition is thought to correspond to a progression of behavioral control from associative to sensorimotor cortico-basal ganglia networks. Habits form following extensive training and are characterized by reduced sensitivity of instrumental responding to reinforcer revaluation; few studies have examined this form of behavioral control in mice. Here we examine the involvement of the dorsolateral and dorsomedial striatum in this transition in the C57BL/6 inbred mouse strain. We provide evidence that damage to the dorsolateral striatum disrupts habitual responding – that is, it preserves sensitivity to changes in outcome value following either outcome devaluation or, for the first time in mice, outcome inflation. Together, these data show that instrumental responding in lesioned mice tracks the current value of a reinforcer and provide evidence that neuroanatomical mechanisms underlying habit learning in rats are preserved in mouse. This will allow for genetic and molecular dissection of neural factors involved in decision-making and mechanisms of aberrant habit formation.

The hippocampus is essential for the consolidation of some explicit long-term memories, including trace conditioning. Lesions and pharmacological manipulations of the dorsal hippocampus (DH) have provided strong evidence for its involvement in the acquisition and expression of trace fear memories. However, no studies have specifically targeted DH subregions [CA1 and dentate gyrus (DG)] to determine their involvement in trace fear conditioning. In the present study, rats received bilateral cannulation targeting either the DG or CA1 of the DH. Following surgery, animals were trace fear conditioned. Forty-eight hours following training, rats received bilateral infusions of the AMPA/kainate glutamate receptor antagonist, CNQX, or vehicle. Following the infusion, rats were placed in a novel context for the tone test. Rats that received CNQX into the DG froze significantly less during the tone and trace interval as compared to controls. Rats that received CNQX into the DH CA1 showed no difference in freezing during the tone or trace interval as compared to controls. These data support a role for the DG in the expression of trace tone fear conditioning.

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