Hippocampus and contextual fear conditioning: Recent controversies and advances

Abstract

ABSTRACT:Dorsal hippocampal (DH) lesions produce a severe deficit in recently, but not remotely, acquired contextual fear without impairing memory of discrete training stimuli, i.e., DH lesions produce an anterograde and time-limited retrograde amnesia specific to contextual memory. These data are consistent with the standard model which posits temporary involvement of the hippocampus in recent memory maintenance. However, three recent controversies apparently weaken the case for a selective mnemonic role for the hippocampus in contextual fear. First, although retrograde amnesia (from posttraining lesions) is severe, anterograde amnesia (from pretraining lesions) may be mild or nonexistent. Second, a performance, rather than mnemonic, account of contextual freezing deficits in hippocampal-lesioned animals has been offered. Third, damage to the entire hippocampus, including the ventral hippocampus, can produce a dramatic and temporally stable disruption of context and tone fear. These data are reviewed and explanations are offered as to why they do not necessarily challenge the standard model of hippocampal memory function in contextual fear. Finally, a more complete description of the hippocampus' proposed role in contextual fear is offered, along with new data supporting this view. In summary, the data support a specific mnemonic role for the DH in the acquisition and consolidation of contextual representations. Hippocampus 2001;11:8 -17.

Temporary inhibition of dorsal or ventral hippocampus by muscimol: Distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning

“…In the fear conditioning experiments (Experiment 2 and 3), we aimed to corroborate our previous finding that ventral hippocampal muscimol (1 µg / 0.5 µl / side) disrupts contextual, but not tone, fear conditioning (Bast et al, 2001a) and to extend this finding by demonstrating similar effects of dorsal hippocampal muscimol. Such an outcome would be consistent with the idea that contextual fear conditioning requires dorsal hippocampal mechanisms mediating the formation of context representations, and ventral hippocampal mechanisms relating the context representations to fear processing via subcortical structures, including the amygdala (Maren and Fanselow, 1995;Anagnostaras et al, 2001;Bast et al, 2001a;Bannerman et al, 2004;Fanselow & Dong, 2010). While the ventral hippocampus has also been implicated in tone fear conditioning (Bast et al, 2001b;Bannerman et al, 2004), ventral hippocampal muscimol did not significantly reduce tone fear conditioning in our previous study (even though there was a numerical reduction), and we argued that partial inhibition of neuronal activity in the ventral hippocampus via GABA-A receptor stimulation may not sufficiently interfere with ventral hippocampal processing to affect tone fear conditioning (in contrast, more general ventral hippocampal inactivation by the sodium channel blocker tetrodotoxin markedly impaired tone fear conditioning) (Bast et al, 2001a).…”

“…Studies examining the effects of lesion or pharmacological manipulations of the hippocampus in rats have provided compelling evidence that the hippocampus is important for unconditioned anxiety/fear responses, as well as the formation and expression of conditioned fear responses to elemental (e.g., auditory) and contextual stimuli 1 Moreover, the weight of evidence from studies using separate ventral or dorsal hippocampal manipulations suggests that the ventral hippocampus plays a rather general role in unconditioned anxiety and conditioned fear, whereas dorsal hippocampal contributions are more restricted to specific mnemonic aspects of fear conditioning, such as context learning; this is consistent with the ventral hippocampus featuring stronger direct connectivity to amygdala and hypothalamus, key components of the brain's anxiety and fear circuit, whereas the dorsal hippocampus is more closely linked to parts of the entorhinal cortex that are implicated in visuo-spatial information encoding (Moser & Moser, 1998;Anagnostaras et al, 2001;Bast et al, 2001b;Kjelstrup et al, 2002;Bannerman et al, 2004;Maren & Holt, 2004;Pentkowski, et al, 2006;Bast, 2007;Engin & Treit, 2007;Fanselow & Dong, 2010;Bast, 2011). …”

“…The weight of evidence from studies using partial hippocampal cytotoxic lesions or temporary inactivation suggests that both ventral and dorsal hippocampus play a role in forming conditioned fear memories, with the effects of dorsal hippocampal lesions or inactivation largely limited to contextual fear memory (Anagnostaras et al, 2001;Bast et al, 2001aBast et al, , 2001bBannerman et al, 2004;Maren & Holt, 2004;Pentkowski, et al, 2006;Esclassan et al, 2009). …”

Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence

“…cues and temporal or episodic context (e.g. Sharp 1999;Anagnostaras et al 2001;Moser and Paulsen 2001;Anderson and Jeffery 2003). So-called hippocampal "place" cells are critical in the formation of "maps" or representations of all of these distinct contextual elements (Wood et al 2000;Moser and Paulsen 2001).…”

Cancer chemotherapy impairs contextual but not cue-specific fear memory

“…The specific deficits in contextual fear memory observed in this study suggest that chemotherapy may have detrimental effects on the hippocampus. Indeed, previous studies provide substantial evidence that the hippocampus plays a critical role in contextual fear conditioning [1,7,13,19,20]. In a signaled shock preparation such as the one used here, in which a discrete stimulus precedes the occurrence of footshock, contextual conditioning has been shown to be particularly sensitive to hippocampal damage [23].…”