Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats

Abstract

Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments 1 and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system.

Chronic Morphine Selectively Impairs Cued Fear Extinction in Rats: Implications for Anxiety Disorders Associated with Opiate Use

“…Second, it is possible that chronic opiate exposure interacts with the induction of LTP at some hippocampal synapses, but leaves LTP at other synapses intact. Third, hippocampal lesions do not invariably produce deficits in learning and memory for contextual fear (Maren et al, 1997;Phillips and LeDoux, 1994), and contextual fear conditioning can be acquired in the absence of an intact hippocampus (Wiltgen et al, 2006).…”

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

“…The DH is not necessary for explicit CS-US or 'foreground' contextual conditioning since post-training DH lesions or inactivation fail to impair conditioned fear both to explicit (Kim and Fanselow, 1992;Maren et al, 1997) and contextual CSs paired directly with shock (Phillips and LeDoux, 1994), and fail to impair contextual discrimination performance (Good and Honey, 1991). In contrast, the integrity of the DH is necessary for 'background' contextual fear conditioning, since post-training DH lesions abolish conditioned fear to a context that previously served as a background to CS-shock pairings and impair context-dependent latent inhibition to an explicit CS (Kim and Fanselow, 1992;Phillips and LeDoux, 1994;Maren et al, 1997;Holt and Maren, 1999). The DH interacts with subcortical brain regions via its output structure, the dorsal subiculum (Jay et al, 1992;Ferbinteanu and McDonald, 2001).…”

Cancer chemotherapy impairs contextual but not cue-specific fear memory

“…Rats were trained in a signaled fear conditioning paradigm used previously [3,20]. During the training session, rats received three trials each consisting of a 10-s presentation of the tone followed immediately by footshock (1 mA, 1 s).…”

“…Cued fear memory was tested 24 h after the context test by reexposing the rats to the tone (twenty 10-s trials) in a new context (no shock was delivered). This paradigm is particularly useful since the neural circuitry underlying cue-specific and contextual conditioned fear is already well established [20]. In addition, since training takes place in a single session and is followed by distinct test sessions, it is possible to gain insight into the specific phases and nature of mnemonic function that may be affected.…”