Prefrontal cortical mechanisms underlying delayed alternation in mice

Abstract

HH. Prefrontal cortical mechanisms underlying delayed alternation in mice. J Neurophysiol 108: 1211-1222, 2012. First published April 25, 2012 doi:10.1152/jn.01060.2011The prefrontal cortex (PFC) has been implicated in the maintenance of task-relevant information during goal-directed behavior. Using a combination of lesions, local inactivation, and optogenetics, we investigated the functional role of the medial prefrontal cortex (mPFC) in mice with a novel operant delayed alternation task. Task difficulty was manipulated by changing the duration of the delay between two sequential actions. In experiment 1, we showed that excitotoxic lesions of the mPFC impaired acquisition of delayed alternation with long delays (16 s), whereas lesions of the dorsal hippocampus and ventral striatum, areas connected with the PFC, did not produce any deficits. Lesions of dorsal hippocampus, however, significantly impaired reversal learning when the rule was changed from alternation to repetition. In experiment 2, we showed that local infusions of muscimol (an agonist of the GABA A receptor) into mPFC impaired performance even when the animal was well trained, suggesting that the mPFC is critical not only for acquisition but also for successful performance. In experiment 3, to examine the mechanisms underlying the role of GABAergic inhibition, we used Cre-inducible Channelrhodopsin-2 to activate parvalbumin (PV)-expressing GABAergic interneurons in the mPFC of PV-Cre transgenic mice as they performed the task. Using whole cell patch-clamp recording, we demonstrated that activation of PV-expressing interneurons in vitro with blue light in brain slices reliably produced spiking and inhibited nearby pyramidal projection neurons. With similar stimulation parameters, in vivo stimulation significantly impaired delayed alternation performance. Together these results demonstrate a critical role for the mPFC in the acquisition and performance of the delayed alternation task. channelrhodopsin; interneuron; operant; optogenetics; parvalbumin THE PREFRONTAL CORTEX (PFC) is widely thought to be involved in higher cognitive functions, as shown by studies in primates (Castner et al.

Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity

“…Indeed, prelimbic (PL) and infralimbic (IL) parts of mPFC receive direct input from CA1 region of HC2223, and there also exist indirect connections between PL/IL and HC via nucleus reuniens (NRe) in midline thalamus2425. Lesions in mPFC hardly affect spatial memory functions proper, but rather impair the flexibility of MWM performance26272829303132, which is consistent with a more general function of mPFC in executive control, decision making, and most notably, cognitive flexibility333435.…”

A GABAergic nigrotectal pathway for coordination of drinking behavior

“…Cannulae implantation and drug infusions were performed as previously described 43 . Briefly, mice were anesthetized and steel cannulae (24 GA, 3 mm length below pedestal, Plastics One) were implanted at a 15 ° angle relative to the dorsoventral axis targeting the final coordinates, −3.5 AP, 1.85 ML and −1.8 DV (from dura).…”

Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia

“…In this study, we employed the delayed alternation variant of the Y maze task (Rossi et al, 2012). All mice learned to complete the spatial discrimination task with a 90% criterion level of alternation within the 7 day training session with no overall difference in performance between genotypes (Fig.…”