Effects of exercise and environmental complexity on deficits in trace and contextual fear conditioning produced by neonatal alcohol exposure in rats.

In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9 followed by either free access to a running wheel on PD 30-41 and housing in a complex environment on PD 42-72 (wheel-running plus environmental complexity; WREC) or conventional social housing (SHSH) from PD 30 to 72. Adult rats (PD 80 ± 5) received 5 trials/day of a 10-s flashing-light conditioned stimulus (CS) paired with .8 mA footshock either immediately (delay conditioning) or after a 10-s trace interval (trace conditioning) for 2 days. Neonatal alcohol exposure impaired context and trace conditioning, but not short-delay conditioning. The WREC intervention did not reverse these deficits, despite increasing context-related freezing in ethanol-exposed and SI animals.

Egr-1 mRNA expression patterns in the prefrontal cortex, hippocampus, and amygdala during variants of contextual fear conditioning in adolescent rats.

We report activation of the immediate-early gene Egr-1 in the lateral amygdala (LA), hippocampus (CA1), and medial prefrontal cortex (mPFC) 30-min following the training phase in the context pre-exposure facilitation effect (CPFE) and standard context fear conditioning (180 s context exposure→shock). On day one of the CPFE paradigm, postnatal day (PD) 31 rats (±1) were pre-exposed to Context A (Pre) or Context B (Alt-Pre) for 5 min followed by five additional 1-min exposures. A day later, Pre and Alt-Pre rats received a 2-s, 1.5 mA footshock immediately upon placement in Context A. Animals included in in situ hybridization were then sacrificed 30 (±3) min later. On day three, the behaviorally-tested Pre rats showed significantly more fear-conditioned freezing in Context A than Alt-Pre rats. Standard context fear conditioning groups showed much greater freezing than the Pre group, as well as no shock and immediate-shock controls. Thirty minutes after immediate shock training, Pre rats showed increased Egr-1 mRNA in the prelimbic mPFC relative to Alt-Pre rats. Standard context conditioning selectively increased Egr-1 in CA1. In the LA and mPFC, Egr-1 increased to a similar extent in no shock, immediate shock, and standard context conditioning relative to homecage controls. The present study demonstrates that Egr-1 mRNA expression has a complex relationship to fear learning in different brain regions and variants of context conditioning.

Determinants of novel object and location recognition during development.

In the novel object recognition (OR) paradigm, rats are placed in an arena where they encounter two sample objects during a familiarization phase. A few minutes later, they are returned to the same arena and are presented with a familiar object and a novel object. The object location recognition (OL) variant involves the same familiarization procedure but during testing one of the familiar objects is placed in a novel location. Normal adult rats are able to perform both the OR and OL tasks, as indicated by enhanced exploration of the novel vs. the familiar test item. Rats with hippocampal lesions perform the OR but not OL task indicating a role of spatial memory in OL. Recently, these tasks have been used to study the ontogeny of spatial memory but the literature has yielded conflicting results. The current experiments add to this literature by: (1) behaviorally characterizing these paradigms in postnatal day (PD) 21, 26 and 31-day-old rats; (2) examining the role of NMDA systems in OR vs. OL; and (3) investigating the effects of neonatal alcohol exposure on both tasks. Results indicate that normal-developing rats are able to perform OR and OL by PD21, with greater novelty exploration in the OR task at each age. Second, memory acquisition in the OL but not OR task requires NMDA receptor function in juvenile rats [corrected]. Lastly, neonatal alcohol exposure does not disrupt performance in either task. Implications for the ontogeny of incidental spatial learning and its disruption by developmental alcohol exposure are discussed.