Dorsal versus ventral hippocampal contributions to trace and contextual conditioning: Differential effects of regionally selective nmda receptor antagonism on acquisition and expression

Abstract

ABSTRACT:The dorsal and ventral subregions of the hippocampus likely play dissociable roles in some forms of learning. For example, we have previously demonstrated that temporary inactivation of ventral, but not dorsal, hippocampus dramatically impaired the acquisition of trace fear conditioning, while temporary inactivation of dorsal, but not ventral, hippocampus impaired spatially guided reinforced alternation (Czerniawski et al. (2009) Hippocampus 19:20-32). Importantly, emerging data suggest that lesions, temporary inactivation, and NMDA receptor antagonism within these subregions can produce quite different patterns of behavioral effects when administered into the same region. Specifically, while neither lesions nor temporary inactivation of dorsal hippocampus impair the acquisition of trace fear conditioning, learning in this paradigm is severely impaired by pre-training administration of the NMDA receptor antagonist dl-2-phosphonovaleric acid (APV) in dorsal hippocampus; the effect of NMDA receptor antagonism within ventral hippocampus on the acquisition and expression of trace conditioning, or on learning in general, has not yet been systematically explored. The present study extends our previous work examining the differential effect of lesions or inactivation of the dorsal and ventral hippocampal subregions by systematically examining the effect of regionally selective pre-training or pre-testing administration of APV on the acquisition and expression of trace and contextual fear conditioning. The results of these studies demonstrate that while pre-training NMDA receptor antagonism within either the dorsal or ventral subregion of the hippocampus impaired the acquisition of both trace and contextual conditioning, pre-testing NMDA receptor antagonism within ventral, but not dorsal, hippocampus impaired the expression of previously-acquired trace and contextual fear conditioning. These data suggest that selectively manipulating the integrity of individual subregions may result in compensatory mechanisms that can support learning, and that NMDA-dependent plasticity within both dorsal and ventral hippocampus is normally required for the acquisition and maintenance of memory in trace and contextual fear conditioning. V

Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning

“…One hour after the test session, all subjects in each group were sacrificed and tissue from both the dorsal and ventral subdivisions of the hippocampus was prepared for Arc protein concentration analysis as described in the General Methods section. We hypothesized that, consistent with previous observations, pre-training infusion of APV would impair expression of memory for trace fear conditioning 24 h later (Czerniawski et al, 2012). We further hypothesized that testing 24 h following acquisition would significantly enhance Arc expression in animals receiving pre-training infusions of aCSF relative to those receiving pre-training infusions of APV.…”

“…Consistent with several previous studies in our laboratory (Czerniawski, Yoon, & Otto, 2009;Czerniawski et al, 2011Czerniawski et al, , 2012Yoon & Otto, 2007), each test session consisted of three trials that were procedurally identical to those used during training, except that the footshock US was not delivered. Although a single test trial is common among studies of memory reactivation (see Nader & Einarsson, 2010), three trials were used in Experiment One in order to obtain a reliable measure of the effect of APV on memory acquisition that could serve as replication for our previous work (Czerniawski et al, 2012), and in Experiment Two so that results from this would be compatible with those from Experiment One. Freezing behavior, defined as a rigid posture and lack of movement except that required for respiration, was recorded throughout the entire testing session by an observer blind to the experimental condition of the subject.…”

“…Importantly, we have also recently shown that the initial acquisition and consolidation of memory for trace fear conditioning is associated with, and critically dependent upon, experience-dependent enhancements of Arc expression within the ventral hippocampus (VH) (Czerniawski et al, 2011). Moreover, both the acquisition of trace fear conditioning and the learning-dependent enhancement of Arc expression can be blocked by pre-training infusion of either the NMDA receptor antagonist APV or Arc antisense oligodeoxynucleotides (ODNs) into VH (Czerniawski, Ree, Chia, & Otto, 2012). With respect to the potential role of Arc in memory reconsolidation, Maddox and Schafe (2011) found that inhibition of Arc translation within the amygdala suppressed the reconsolidation of hippocampal-independent delay fear conditioning.…”

Prefrontal Activity Links Nonoverlapping Events in Memory

“…PL receives diverse input from cortical and subcortical regions and another structure, such as the hippocampus, likely provides the signal necessary to initiate bridging activity in PL. Not only is the hippocampus necessary for trace conditioning (McEchron et al, 1998;Czerniawski et al, 2012), but hippocampal units show learning-related activity during the CS (Gilmartin and McEchron, 2005b). Determining the functional significance of temporally specific input to PL on bridging activity and memory formation is now possible with optogenetic approaches.…”

Transient Inactivation of the Neonatal Ventral Hippocampus Impairs Attentional Set-Shifting Behavior: Reversal with an α7 Nicotinic Agonist

“…Functional distinctions between the dorsal and ventral subregions of the hippocampus persist through adulthood. Using local infusions of NMDA antagonists in adult rats, Otto and colleagues have demonstrated dissociable roles of the two subregions in other forms of learning including, trace fear conditioning, contextual conditioning, and spatially guided alternation (Czerniawski et al, 2009(Czerniawski et al, , 2011.…”