Animal models of prefrontal-executive function.

Abstract

Executive function allows us to interact with the world in a purposive, goal-directed manner. It relies on several cognitive control operations that are mediated by different regions of the prefrontal cortex. While much of our knowledge about the functional subdivisions of the prefrontal cortex comes from the systematic assessment of patients with brain damage, animal models have served as the predominant tool for investigating specific structure-function relationships within the prefrontal cortex, especially as they relate to complex executive behaviors. These studies generally involve the targeted disruption of neural circuits combined with behavioral testing using carefully designed cognitive paradigms. In this review, I will describe a broad range of such experiments conducted in rats and monkeys that together reveal the distinct contributions of dorsal, medial, and ventral prefrontal cortex to different aspects of executive function. The effects of lesions and local pharmacological manipulations have provided valuable insights into the neural underpinnings of executive function and its neurochemical modulation. Despite the challenges associated with establishing a precise homology between animal models of prefrontal function and the human brain, such models currently offer the best means to systematically investigate the cognitive building blocks of executive function. This helps define the neural circuits that lead to a range of neurological and psychiatric disorders and facilitate the development of effective therapeutic strategies to ameliorate the associated cognitive impairments.

Comparisons of 9-Tetrahydrocannabinol and Anandamide on a Battery of Cognition-Related Behavior in Nonhuman Primates

“…The present studies were not designed to assess localization of function under the different cognitive tasks, but previous research may inform the current findings. For example, the control of discrimination reversal performance appears to be highly localized in the orbital prefrontal cortex (reviewed in Chudasama, 2011), whereas DMTS is thought to be closely controlled by hippocampal mechanisms (reviewed in Eichenbaum et al, 1992). Although CB 1 receptors are widely expressed throughout the brain (Freund et al, 2003), recent studies have indicated that CB 1 receptor dynamics (e.g., desensitization and downregulation) differ across brain regions (see Lazenka et al, 2013) and showed that following discontinuation cannabinoidinduced decreases in CB 1 receptor function persisted relatively longer and CB 1 receptor signaling recovered more quickly in the striatum compared with the hippocampus.…”

Hippocampal-Prefrontal Cortical Circuit Mediates Inhibitory Response Control in the Rat

“…Inhibitory control deficits take multiple forms, such as the compulsive repetition of responses or the failure to withhold an impulsive act. Rats and mice with excitotoxic lesions of the vPFC (or subregions thereof) exhibit difficulty in tasks that require the active suppression of inappropriate responses (for review, see Chudasama, 2011;Dalley et al, 2011). Lesions to the hippocampus, a structure that is most often associated with spatial memory, also affect behavioral control.…”

Medial prefrontal lesions in mice impair sustained attention but spare maintenance of information in working memory

“…Since this early study, a better understanding of the cognitive deficits produced in rats with lesions or with dopaminergic or cholinergic perturbations of the PFC has been achieved using other operant-based paradigms. This work has been comprehensively reviewed elsewhere (Dalley et al 2004;Chudasama 2011). One such operant-based paradigm, the combined attention and memory (CAM) task was designed to isolate attentional from memory processes in rats within individual trials (Chudasama and Robbins 2004).…”