Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

Abstract

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.

Neuronal activity in primate auditory cortex during the performance of audiovisual tasks

“…The present study confirms and extends previous findings that neuronal activity in auditory cortex is task‐dependent (Brechmann & Scheich, ; Scheich & Brosch, ; Alho et al ., ). In agreement with previous studies we found that, during task engagement, neurons in auditory cortex responded to non‐auditory stimuli that were relevant for the task, such as light flashes and a drop of water (Brosch et al ., ; Bigelow et al ., ; Li et al ., ), that responses to auditory stimuli could differ between tasks (Hocherman et al ., ; Miller et al ., ; Otazu et al ., ), and that neuronal firing rates could slowly increase or decrease for several seconds during various phases of the tasks.…”

“…water (Brosch et al, 2005;Bigelow et al, 2014;Li et al, 2014), that responses to auditory stimuli could differ between tasks (Hocherman et al, 1976;Miller et al, 1980;Otazu et al, 2009), and that neuronal firing rates could slowly increase or decrease for several seconds during various phases of the tasks. The main difference from our previous study in which monkeys had to categorise the direction of frequency steps (Brosch et al, 2011a) was that in the current study we did not find firing that was related to reward expectation and reward prediction errors.…”

“…Auditory responses may also depend on the type of association between sound and reward (Beaton & Miller, 1975;David et al, 2012), on sound anticipation (Hocherman & Yirmiya, 1990;Jaramillo & Zador, 2011), and on audio-motor associations (Schafer & Marcus, 1973;M€ uller-Preuss & Ploog, 1981;Vaadia et al, 1982;Curio et al, 2000;Eliades & Wang, 2003. During task engagement auditory cortical neurons may also respond to non-auditory stimuli or to the reward (Brosch et al, 2005;Li et al, 2014). In addition to these phasic responses, we have recently described slow increases or decreases in firing, on a time scale of seconds, that emerge during a categorisation task (Brosch et al, 2011a,b).…”

Unconsciously Implanted Visuoauditory Memory in the Presence of Cholecystokinin Retrieved in Behavioral Contexts

“…Previously, we established a long-term visuoauditory associative memory in rats critically dependent on the entorhinal cortex by pairing a visual stimulus (VS) with electrical stimulation of the auditory cortex 11 .Many neurons in the entorhinal cortex contain cholecystokinin (CCK) [12][13][14] . They project to and enable long-term potentiation (LTP) in the auditory cortex by responding to a formerly ineffective sound or light stimulus after pairing with a noise-burst stimulus 15 . Infusion of a CCK antagonist into the auditory cortex prevents the formation of this visuoauditory association, similar to inactivation of the entorhinal cortex 11,15 .In this study, we aimed to confirm the formation of visuoauditory associative memory between sound and light stimuli.…”

“…They project to and enable long-term potentiation (LTP) in the auditory cortex by responding to a formerly ineffective sound or light stimulus after pairing with a noise-burst stimulus 15 . Infusion of a CCK antagonist into the auditory cortex prevents the formation of this visuoauditory association, similar to inactivation of the entorhinal cortex 11,15 .In this study, we aimed to confirm the formation of visuoauditory associative memory between sound and light stimuli. To test our hypothesis that CCK is a memory-writing chemical for visuoauditory memory in the neocortex, we determined whether the presence of CCK allowed implantation of a memory in the cortex of anesthetized rats retrievable in a behaviorally relevant context.…”