Differential Role of Muscarinic Transmission within the Entorhinal Cortex and Basolateral Amygdala in the Processing of Irrelevant Stimuli

Abstract

Cholinergic projections to the entorhinal cortex (EC) and basolateral amygdala (BLA) mediate distinct cognitive processes through muscarinic acetylcholine receptors (mAChRs). In this study, we sought to further differentiate the role of muscarinic transmission in these regions in cognition, using the latent inhibition (LI) phenomenon. LI is a cross-species phenomenon manifested as poorer conditioning to a stimulus experienced as irrelevant during an earlier stage of repeated non-reinforced pre-exposure to that stimulus, and is considered to index the ability to ignore, or to in-attend to, irrelevant stimuli. Given our recent findings that systemic administration of the mAChR antagonist scopolamine can produce two contrasting LI abnormalities in rats, ie, abolish LI under conditions yielding LI in non-treated controls, or produce abnormally persistent LI under conditions preventing its expression in non-treated controls, we tested whether mAChR blockade in the EC and BLA would induce LI abolition and persistence, respectively. We found that intra-EC scopolamine infusion (1, 10 mg per hemisphere) abolished LI when infused in pre-exposure or both pre-exposure and conditioning, but not in conditioning alone, whereas intra-BLA scopolamine infusion led to persistent LI when infused in conditioning or both stages, but not in pre-exposure alone. Although cholinergic innervation of the EC and BLA has long been implicated in attention to novel stimuli and in processing of motivationally significant stimuli, respectively, our results provide evidence that EC mAChRs also have a role in the development of inattention to stimuli, whereas BLA mAChRs have a role in re-attending to previously irrelevant stimuli that became motivationally relevant.

β-Adrenergic receptors in the insular cortex are differentially involved in aversive vs. incidental context memory formation

“…2) as well as in a parallel process required to relate a previously inconsequential stimulus (i.e., context during pre-exposure) to a US (i.e., aversive footshock during conditioning), but are not necessary for the formation of an incidental memory (familiarization) of the inconsequential stimulus (i.e., dark compartment context) before it is paired with a US (i.e., footshock). This interpretation of our observations is consistent with a body of evidence suggesting that the IC contributes to a multibrain region complex activity that produces contrasting effects during different stages of stimulus pre-exposure (Roesler et al 2005;Malin and McGaugh 2006;Miranda and Bermudez-Rattoni 2007;Barak and Weiner 2010). Hence, in accordance with previous evidence, we infer that intra-IC propranolol infusions in the present experiments affected the capacity to subsequently process information acquired during a prior inconsequential experience, in a manner that disrupted the mechanism needed to respond to the changed stimulus properties during conditioning, namely its new association with a US.…”

“…Hence, in accordance with previous evidence, we infer that intra-IC propranolol infusions in the present experiments affected the capacity to subsequently process information acquired during a prior inconsequential experience, in a manner that disrupted the mechanism needed to respond to the changed stimulus properties during conditioning, namely its new association with a US. This interpretation is in line with evidence that certain structures are important for altering responses based upon changes in stimulus-consequence associations, an aspect of cognitive flexibility (Hatfield et al 1996;Malkova et al 1997;Baxter et al 2000;Cooper and Mizumori 2001;Schoenbaum et al 2003;Malin and McGaugh 2006;Barak and Weiner 2010).…”

Dissociating scopolamine-induced disrupted and persistent latent inhibition: stage-dependent effects of glycine and physostigmine

“…Thus, low scopolamine doses (0.15 or 0.5 mg/kg) disrupted LI by an action in the pre-exposure stage, whereas a higher dose (1.5 mg/kg) produced abnormally persistent LI via action in the conditioning stage (Barak 2009; Barak andWeiner 2007, 2009). Stagespecific action on LI was also obtained with intracerebral scopolamine infusion, with infusion into the entorhinal cortex before pre-exposure but not conditioning disrupting LI and infusion into the basolateral amygdala before conditioning but not pre-exposure inducing LI persistence (Barak 2009;Barak and Weiner 2010). Pharmacologically, the distinction between the two LI abnormalities was supported by their distinct response to antipsychotic drugs (APDs), with LI disruption reversed by the typical APD haloperidol and the atypical APD clozapine and LI persistence being resistant to both of these APDs (Barak 2009;Barak andWeiner 2007, 2009).…”

Muscarinic Receptors Modulate the Intrinsic Excitability of Infralimbic Neurons and Consolidation of Fear Extinction

“…In the intra-IL experiments, the age of the rats ranged between 38 to 42 days old at the time of extinction training. The dose of Scop was based on similar behavioral studies that infused Scop into the prefrontal cortex, perirhinal cortex, amygdala, and/or hippocampal formation regions (Herremans et al, 1996;Barros et al, 2001;Warburton et al, 2003;Winters et al, 2006;Barak and Weiner, 2010). Drugs were infused at a rate of 0.5 ml for 1 min.…”