Learning-Induced Enduring Changes in Functional Connectivity among Prefrontal Cortical Neurons

Abstract

Current thinking about how memories are stored in the brain has been profoundly influenced by Donald O. Hebb's cell assembly hypothesis, which posits that (1) learning produces a stable alteration in patterns of connectivity among repeatedly coactivated neurons, and (2) memory retrieval involves reactivation of those altered patterns of connectivity. However, learning-induced changes in connectivity that persist over long periods of time have not been clearly demonstrated. In the present study, two spatial navigation tasks and a long-term ensemble recording technique are used to describe long-lasting modifications in functional connectivity (FC) (defined as changes in synchronous firing) of prefrontal cortical neurons in behaving rats. Animals were initially trained to alternate visiting two spatial locations on a figure-8-shaped maze to obtain a reward (alternating task 1). Afterward, while continuing on task 1, animals were additionally trained to visit only one spatial location on the same maze to obtain a reward (unilateral task 2). Multiple single units were recorded while rats were undergoing acquisition, retention, and performance of both tasks. Our data indicate that correlated firing of prefrontal cortical neurons changed significantly in early phases of training when learning rate was maximal but became progressively smaller in later phases when learning reached asymptote. After animals became proficient, FC remained constant, although neuronal activities varied across two different tasks. The present finding of negatively accelerated changes in FC confirms associative learning theories and provides crucial neurophysiological evidence for Hebb's hypothesis.

Cortical network functional connectivity in the descent to sleep

“…In addition, activity dependent changes in synaptic weighting are believed to underlie experiential learning throughout the life span, promoting the dynamic reconfiguration of neural networks to meet changing sensorimotor and cognitive processing demands (40)(41)(42). Sleep, particularly deep slow wave sleep, has been posited to represent a mechanism by which changes in synaptic weighting accumulated in wakefulness are homeostatically normalized (43,44).…”

Prefrontal cortex and hippocampus subserve different components of working memory in rats

“…For instance, damage to the PFC produces impairments in various working memory tasks in humans and non-human primates (Kolb 1990;Fuster 1997;Stuss and Alexander 2000). Additionally, recording and brain imaging studies found neural activity correlates of working memory, i.e., increased PFC activity during the delay period (Fuster and Alexander 1971;Kubota and Niki 1971;Funahashi et al 1989).In rodents, a delayed alternation task (DAT; employing T, radial-arm, and figure-eight mazes) has been widely used to further investigate the PFC-working memory hypothesis (Murphy et al 1996;Zahrt et al 1997;Baeg et al 2003Baeg et al , 2007Schoenbaum et al 2003;Birnbaum et al 2004;Clinton et al 2006). In this task, the animal is typically cued (via a discrete or spatial stimulus) to make a choice response to obtain a reward, but is prevented from responding until after some delay period (or working memory demand) has been imposed.…”

“…In rodents, a delayed alternation task (DAT; employing T, radial-arm, and figure-eight mazes) has been widely used to further investigate the PFC-working memory hypothesis (Murphy et al 1996;Zahrt et al 1997;Baeg et al 2003Baeg et al , 2007Schoenbaum et al 2003;Birnbaum et al 2004;Clinton et al 2006). In this task, the animal is typically cued (via a discrete or spatial stimulus) to make a choice response to obtain a reward, but is prevented from responding until after some delay period (or working memory demand) has been imposed.…”

Stimulus-induced reduction of noise correlation in rat prefrontal cortex

“…Twelve tetrodes were implanted in the medial prefrontal cortex, and single units were recorded from the prelimbic and infralimbic cortex. Putative single units were isolated off-line by manual cluster cutting of various spike waveform parameters [19]. The experimental protocol was approved by the Institutional Animal Care and Use Committee of the Ajou University School of Medicine.…”