Action control is mediated by prefrontal BDNF and glucocorticoid receptor binding.

Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences.

Dissociable regulation of instrumental action within mouse prefrontal cortex.

Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue-related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber.

Prelimbic cortex bdnf knock-down reduces instrumental responding in extinction.

Anatomically selective medial prefrontal cortical projections regulate the extinction of stimulus-reinforcement associations, but the mechanisms underlying extinction of an instrumental response for reward are less well-defined and may involve structures that regulate goal-directed action. We show brain-derived neurotrophic factor (bdnf) knock-down in the prelimbic, but not orbitofrontal, cortex accelerates the initial extinction of instrumental responding for food and reduces striatal BDNF protein. When knock-down mice were provided with alternative response options to readily obtain reinforcement, extinction of the previously reinforced response was unaffected, consistent with the hypothesis that the prelimbic cortex promotes instrumental action, particularly when reinforcement is uncertain or unavailable.

Prior chronic cocaine exposure in mice induces persistent alterations in cognitive function.

Chronic cocaine use has been proposed to induce long-lasting alterations in cognitive functions dependent on the prefrontal cortex, and these alterations may contribute to the development of addiction. However, the underlying cellular mechanisms remain largely unknown, in part because of the lack of suitable animal models of cocaine-induced cognitive dysfunction that are amenable to molecular manipulations. Here, we characterized the effects of repeated cocaine administration on multiple aspects of cognitive function in C57BL/6 mice.

Acute hippocampal brain-derived neurotrophic factor restores motivational and forced swim performance after corticosterone.

Background: Alterations in cellular survival and plasticity are implicated in the neurobiology of depression, based primarily on the characterization of antidepressant efficacy in naïve rodents rather than on models that capture the debilitating and protracted feelings of anhedonia and loss of motivation that are core features of depression.

Methods: In adult male mice, we evaluated persistent effects of oral corticosterone (CORT) exposure on anhedonic-like behavior, immobility in the forced swim test (FST), motivational performance in the progressive ratio task, and later endogenous CORT secretion. After verifying long-term decreases in hippocampal brain-derived neurotrophic factor (BDNF) and cAMP Response Element Binding protein phosphorylation (pCREB), the ability of direct hippocampal BDNF microinfusion after CORT exposure to reverse deficits was investigated.

Assessment of cognitive function in the heterozygous reeler mouse.

Rationale: The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function, has yet to be determined.

Objective: Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients.