Dataset Information

Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex.

ABSTRACT: The prefrontal cortex (PFC) regulates cognitive processes critical for goal-directed behavior. PFC cognitive dysfunction is implicated in multiple psychopathologies, including attention deficit hyperactivity disorder (ADHD). Although it has long been known that corticotropin-releasing factor (CRF) and CRF receptors are prominent in the PFC, the cognitive effects of CRF action within the PFC are poorly understood. The current studies examined whether CRF receptor activation in the PFC modulates cognitive function in rats as measured in a delayed response task of spatial working memory. CRF dose-dependently impaired working memory performance when administered either intracerebroventricularly (ICV) or directly into the PFC. The working memory actions of CRF in the PFC were topographically organized, with impairment observed only following CRF infusions into the caudal dorsomedial PFC (dmPFC). Additional studies examined whether endogenous CRF modulates working memory. Both ICV and intra-dmPFC administration of the nonselective CRF antagonist, D-Phe-CRF, dose-dependently improved working memory performance. To better assess the translational potential of CRF antagonists, we examined the cognitive effects of systemic administration of the CRF1 receptor selective antagonist, NBI 35965. Similar procognitive actions were observed in these studies. These results are the first to demonstrate that CRF acts in the PFC to regulate PFC-dependent cognition. Importantly, the ability of CRF antagonists to improve working memory is identical to that seen with all approved treatments for ADHD. These observations suggest that CRF antagonists may represent a novel approach for the treatment of ADHD and other disorders associated with dysregulated prefrontal cognitive function.

SUBMITTER: Hupalo S

PROVIDER: S-EPMC5026742 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex.

Hupalo Sofiya S Berridge Craig W CW

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20160608 11

The prefrontal cortex (PFC) regulates cognitive processes critical for goal-directed behavior. PFC cognitive dysfunction is implicated in multiple psychopathologies, including attention deficit hyperactivity disorder (ADHD). Although it has long been known that corticotropin-releasing factor (CRF) and CRF receptors are prominent in the PFC, the cognitive effects of CRF action within the PFC are poorly understood. The current studies examined whether CRF receptor activation in the PFC modulates c ...[more]

PMID: 27272767

Similar Datasets

Project description:Working memory (WM) provides the stability necessary for high-level cognition. Influential theories typically assume that WM depends on the persistence of stable neural representations, yet increasing evidence suggests that neural states are highly dynamic. Here we apply multivariate pattern analysis to explore the population dynamics in primate lateral prefrontal cortex (PFC) during three variants of the classic memory-guided saccade task (recorded in four animals). We observed the hallmark of dynamic population coding across key phases of a working memory task: sensory processing, memory encoding, and response execution. Throughout both these dynamic epochs and the memory delay period, however, the neural representational geometry remained stable. We identified two characteristics that jointly explain these dynamics: (1) time-varying changes in the subpopulation of neurons coding for task variables (i.e., dynamic subpopulations); and (2) time-varying selectivity within neurons (i.e., dynamic selectivity). These results indicate that even in a very simple memory-guided saccade task, PFC neurons display complex dynamics to support stable representations for WM.SIGNIFICANCE STATEMENT Flexible, intelligent behavior requires the maintenance and manipulation of incoming information over various time spans. For short time spans, this faculty is labeled "working memory" (WM). Dominant models propose that WM is maintained by stable, persistent patterns of neural activity in prefrontal cortex (PFC). However, recent evidence suggests that neural activity in PFC is dynamic, even while the contents of WM remain stably represented. Here, we explored the neural dynamics in PFC during a memory-guided saccade task. We found evidence for dynamic population coding in various task epochs, despite striking stability in the neural representational geometry of WM. Furthermore, we identified two distinct cellular mechanisms that contribute to dynamic population coding.

Dataset Information

Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex.

Publications

Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure