NMDA receptor antagonism disrupts acquisition and retention of the context preexposure facilitation effect in adolescent rats

Developmental Psychobiology

2019

Self Cite

The ontogeny and NMDA‐receptor (NMDAR) mechanisms of context conditioning were examined during standard contextual fear conditioning (sCFC) – involving context and context‐shock learning in the same trial – as a comparison with our previous reports on the Context Preexposure Facilitation Effect (CPFE), which separates these two types of learning by 24 hr. In Experiment 1, systemic administration of the NMDAR antagonist, MK‐801, prior to conditioning disrupted retention but not post‐shock freezing during sCFC in PD31 rats. Experiment 2 replicated and extended this effect to PD17 versus PD31 rats. Consistent with Experiment 1, pre‐training MK‐801 spared post‐shock freezing but impaired retention freezing in PD31 rats. In contrast, pre‐training MK‐801 disrupted post‐shock freezing in PD17 rats, which showed no retention freezing regardless of drug. These results reveal developmental differences in the role of NMDAR activity in the acquisition versus retention of a context‐shock association during sCFC in pre‐weanling and adolescent rats.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

See 2 more Smart Citations

NMDA receptors and the ontogeny of post‐shock and retention freezing during contextual fear conditioning

Miller

Developmental Psychobiology

2019

Self Cite

“…Fear conditioning occurred in four clear Plexiglas chambers designated as Context A as described previously (Heroux, Robinson-Drummer, Rosen, & Stanton, 2016; Murawski & Stanton, 2010; Robinson-Drummer et al, 2016). The chambers measured 16.5 × 12.1 × 21.6 cm and were arranged in a 2 × 2 formation on a Plexiglas stand within a fume hood which provided ambient light and background noise.…”

Section: General Methodsmentioning

confidence: 99%

Antagonism of muscarinic acetylcholine receptors in medial prefrontal cortex disrupts the context preexposure facilitation effect

Robinson-Drummer

Neurobiology of Learning and Memory

2017

Cholinergic function plays a role in a variant of context fear conditioning known as the context preexposure facilitation effect (CPFE; Robinson-Drummer, Dokovna, Heroux, & Stanton, 2016). In the CPFE, acquisition of a context representation, the context-shock association, and expression of context fear occur across successive phases, usually 24hr apart. Systemic administration of scopolamine, a muscarinic acetylcholine receptor antagonist, prior to each phase (context preexposure, immediate-shock training, and testing) disrupts the CPFE in juvenile rats (Robinson-Drummer et al., 2016). Dorsal hippocampal (dHPC) cholinergic function contributes significantly to this effect, as local infusion of scopolamine into the dHPC prior to any individual phase of the CPFE produces a disruption identical to systemic administration (Robinson-Drummer et al., 2016). The current experiment extended these findings to another forebrain region implicated in the CPFE, the medial prefrontal cortex (mPFC). Adolescent rats received bilateral infusions of scopolamine (35μg/side) or PBS 10 min before all three phases of the CPFE or only prior to a single phase. Intra-mPFC administration of scopolamine prior to all three phases significantly impaired fear conditioning suggesting that mPFC cholinergic function is necessary for successful CPFE performance. Analyses of the individual infusion days revealed a significant impairment of the CPFE when infusions occurred prior to preexposure or training (i.e. immediate footshock) but not prior to testing. In total, these findings suggests a role of mPFC cholinergic function in in the acquisition and/or consolidation of a contextual representation and the context-shock association but not to retrieval or expression of fear memory. Implications for mPFC involvement in contextual fear conditioning and neurological dysfunction following neonatal alcohol exposure are discussed.

Differential involvement of amygdalar NMDA receptors across variants of contextual fear conditioning in adolescent rats

Miller

Behavioural Brain Research

2019

Self Cite

In standard contextual fear conditioning (sCFC), learning of the context and formation of the context-shock association occur in the same training session whereas in the context preexposure facilitation effect (CPFE) learning the context (preexposure) and the context-shock association (training) are separated by 24 hours. In both procedures conditioned freezing can be measured immediately (post-shock test) or during a 24-hour retention test. In adult rats, disrupting basolateral amygdala (BLA) activity or plasticity during training on sCFC impairs both post-shock and retention freezing [Maren et al, 1996; 1]. This manipulation on the training day of the CPFE disrupts retention freezing but effects on post-shock freezing are unknown [Matus-Amat et al, 2007; 2]. Experiment 1 extended this literature from adult to adolescent rats and to the role of BLA activity and plasticity in post-shock freezing during the CPFE. Intra-BLA infusions of muscimol prior to the training day of the CPFE disrupted both post-shock and retention freezing in Postnatal Day (PD) 31-33 rats. In the second two experiments, intra-BLA infusions of APV prior to training day of sCFC disrupted retention but not post-shock freezing, while infusions of APV prior to training of the CPFE disrupt both post-shock and retention freezing. Our findings suggest that the BLA plasticity plays a different role in the CPFE vs. sCFC. Its role in the CPFE is similar in both adolescent and adult rats, while the role of the BLA in post-shock freezing during sCFC may differ across age or across studies that employ different procedures or parameters.