Infusions of scopolamine in dorsal hippocampus reduce anticipatory responding in an appetitive trace conditioning procedure

Abstract

IntroductionTrace conditioning is impaired by lesions to dorsal hippocampus, as well as by treatment with the muscarinic acetylcholine antagonist scopolamine. However, the role of muscarinic receptors within hippocampus has received little attention.MethodsThe present study examined the effects of intra‐hippocampal infusion of scopolamine (30 µg/side) in an appetitive (2 vs. 10 s) trace conditioning procedure using sucrose pellets as the unconditioned stimulus (US). Locomotor activity (LMA) was examined in a different apparatus.ResultsIntra‐hippocampal scopolamine reduced responding to the 2 s trace conditioned stimulus (CS). Intra‐hippocampal scopolamine similarly depressed responding within the inter‐stimulus interval (ISI) at both 2 and 10 s trace intervals, but there was no such effect in the inter‐trial interval. There was also some overall reduction in responding when the US was delivered; significant at the 10 s but not at the 2 s trace interval. A similar pattern of results to that seen in response to the CS during acquisition was shown drug‐free (in the 5 s post‐CS) in the extinction tests of conditioned responding. LMA was increased under scopolamine.ConclusionsThe results suggest that nonspecific changes in activity or motivation to respond for the US cannot explain the reduction in trace conditioning as measured by reduced CS responding and in the ISI. Rather, the findings of the present study point to the importance of associative aspects of the task in determining its sensitivity to the effects of scopolamine, suggesting that muscarinic receptors in the hippocampus are important modulators of short‐term working memory.

Training on an Appetitive Trace-Conditioning Task Increases Adult Hippocampal Neurogenesis and the Expression of Arc, Erk and CREB Proteins in the Dorsal Hippocampus

“…The DH plays a predominant role in hippocampus-dependent tasks such as contextual fearconditioning, spatial learning, trace-eyeblink-conditioning, etc. The appetitive conditioning is also altered with total inactivation of DH neuronal activity (Pezze et al, 2018), suggesting that the DH plays a crucial role in the appetitive conditioning. In our study, the induced expressions of Arc, pCREB, pErk1, and pErk2 proteins in the DH, after trace-conditioning is in agreement with this concept.…”

Age-related differences in appetitive trace conditioning and novel object recognition procedures

“…An experimental background stimulus was provided by three wall mounted stimulus lights and the house light flashing on (0.5 s) and off (0.5 s), continuously for the duration of the conditioning session. This ‘envelope stimulus’ provided an additional measure of contextual conditioning, as per earlier studies of the neural substrates of trace conditioning conducted in the same laboratory using the same behavioural procedure (Pezze et al, 2015a, Pezze et al, 2017, Pezze et al, 2018).…”

“…We therefore examined responding to the experimental background, over and above any contextual conditioning to the cues provided by the experimental chambers, with a final set of extinction tests conducted 2 weeks after the fifth conditioning session. Following the test format of earlier studies, these used 30 5 s presentations of the flashing light stimulus over 30 min (Pezze et al, 2015a, Pezze et al, 2017, Pezze et al, 2018). The number of nose-pokes was recorded as above.…”

“…In addition to our earlier studies of the neural substrates of TC using an aversive fear conditioning procedure (Cassaday et al, 2005, Pezze et al, 2017) we devised an appetitive food motivated TC procedure to test the generality of the effects of amphetamine (Kantini, Norman, & Cassaday, 2004) and NAc lesions (Cassaday et al, 2005). This was further developed for use in a series of micro-infusion studies: we have recently shown mPFC DA D 1 receptor modulation of appetitive TC (Pezze, Marshall, & Cassaday, 2015), as well as muscarinic receptor modulation in mPFC (Pezze et al, 2017) and hippocampus (Pezze, Marshall, & Cassaday, 2018). However, these intervention studies have to date been conducted on young adult rats and it has yet to be established whether appetitive TC shows sensitivity to age-related decline, as is known to be the case for aversive TC.…”

“…Thus, the present study examined appetitive TC in a repeated measures design over the course of normal aging in naïve rats, using appetitive procedures requiring many learning trials and hence suitable for the repeated testing. Based on our earlier experimental studies (Kantini et al, 2004, Pezze et al, 2015a, Pezze et al, 2017, Pezze et al, 2018), we hypothesised that older rats’ ability to condition over a 2 s trace interval would be reduced and that the timing of their responses within the longer trace interval might be impaired (normally rats come to distribute their responding towards the end of a 10 s trace). This was a longitudinal study in the sense that two groups of rats were examined over a 6 month timeframe; the developmental timepoints examined were from adulthood to early middle age vs from early to late middle age.…”