Functional Reorganization of a Prefrontal Cortical Network Mediating Consolidation of Trace Eyeblink Conditioning

Abstract

The medial prefrontal cortex (mPFC) has been studied for its role in various cognitive functions, but the roles of its subregions remain unclear. We performed tetrode recordings simultaneously from prelimbic (PL) and rostral (rACC) and caudal (cACC) anterior cingulate subregions of the rabbit mPFC to understand their interactions during learning and tests of remote memory retention for whiskersignaled trace eyeblink conditioning. cACC neurons exhibited an innate response to the conditioning stimulus (CS) that rapidly decreased across sessions, suggesting an attentional role for facilitating CS-US associations. rACC neurons from conditioned rabbits exhibited robust responses to the CS that decreased within each session, possibly evaluating its emotional salience. PL neurons exhibited robust persistent activity during the trace interval during tests of remote memory retention, suggesting its involvement in retrieval and execution of a consolidated response. Mechanistically, conditioning was associated with a greater percentage of persistently responsive neurons than neurons from pseudoconditioned control rabbits, and responses differed significantly between trials with and without conditioned responses. Collectively, these responses reflect a functional reorganization of neural activity within the prefrontal network from an attentional mode to one that orchestrates the retrieval and execution of the learned response.

Pretrial functional connectivity differentiates behavioral outcomes during trace eyeblink conditioning in the rabbit

“…Three of the significant post hoc analyses show a significant difference between the right IPN and right hippocampus on day 1. The role of the prelimbic cortex is most robust once learning has been established (Takehara et al 2003;Hattori et al 2014) therefore our post hoc result is counter to what we would expect. Additionally, the left and right hippocampus shows a significant difference with the right IPN on day 10 only.…”

Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning

“…Putative mechanisms for this modification are discussed, including changes in cellular or network properties, neuromodulatory tone, and/or the synaptic efficacy of toneassociated inputs. delay cells; persistent activity; working memory PERSISTENT NEURAL RESPONSES, in which evoked spiking persists beyond stimulus offset, have been observed in the medial prefrontal cortex (mPFC) during tasks that impose a delay interval between stimulus presentation and behavioral response (Baeg et al 2001;Burgos-Robles et al 2009;Fritz et al 2010;Funahashi et al 1989;Fuster 1973;Fuster and Alexander 1971;Gilmartin and McEchron 2005;Gilmartin et al 2013;Hattori et al 2014;Kubota and Niki 1971;Siegel et al 2012). Persistent responses have been observed across stimulus modalities, including auditory (e.g., Baeg et al 2001;Gilmartin and McEchron 2005;Siegel et al 2012), visual (e.g., Funahashi et al 1989Fuster 1973;Miller et al 1996;Procyk and Goldman-Rakic 2006), and somatosensory (whisker stimulation; Hattori et al 2013).…”

“…Although several cellular and network mechanisms have been proposed to modulate persistent spiking Fransen et al 2006;Kalmbach et al 2013;McCormick et al 2003;Wang 2003), the fundamental question of whether such responses are acquired as a result of experience in vivo has not been directly addressed. Only a scarce number of studies have recorded single-neuron activity during the acquisition of tasks thought to rely on persistent responses (Erickson and Desimone 1999; Gilmartin and McEchron 2005;Hattori et al 2014;Miyashita 1988). These authors suggest that persistent responses may not be acquired per se based on session averages or pseudoconditioning.…”

“…Recently, persistent responses have been reported in the mPFC during trace eyeblink conditioned responses (CRs), which require 200 -500ϩ training trials to acquire (Hattori et al 2014;Siegel et al 2012;Siegel and Mauk 2013;TakeharaNishiuchi and McNaughton 2008), providing a window of opportunity to examine the possible evolution of persistent responses early in learning. Trace conditioning consists of paired presentations of an initially neutral conditioned stimulus (CS; such as a tone or light) followed by a stimulus-free trace interval and terminating with a reflexive unconditioned stimulus (US; such as a puff of air to the eye; Fig.…”

Handcrafted Electrocorticography Electrodes for a Rodent Behavioral Model

“…Stablohm wires have been implemented into tetrode technologies to act as low impedance wires and isolate signals of extracellular spikes [49][50][51][52][53]. Other research have also used stablohm wires as recording electrodes in their electrode arrays and implanted into different regions of an animal's brain for neural recordings [54][55][56][57][58][59][60]. Eight different stablohm wires have been supported by California Fine Wire (www.calfinewire.com) based on the variation of the electrical resistance.…”