Hippocampal regulation of context-dependent neuronal activity in the lateral amygdala

Abstract

Pavlovian fear conditioning is a robust and enduring form of emotional learning that provides an ideal model system for studying contextual regulation of memory retrieval. After extinction the expression of fear conditional responses (CRs) is context-specific: A conditional stimulus (CS) elicits greater conditional responding outside compared with inside the extinction context. Dorsal hippocampal inactivation with muscimol attenuates context-specific CR expression. We have previously shown that CS-elicited spike firing in the lateral nucleus of the amygdala is context-specific after extinction. The present study examines whether dorsal hippocampal inactivation with muscimol disrupts context-specific firing in the lateral amygdala. We conditioned rats to two separate auditory CSs and then extinguished each CS in separate and distinct contexts. Thereafter, single-unit activity and conditional freezing were tested to one CS in both extinction contexts after saline or muscimol infusion into the dorsal hippocampus. After saline infusion, rats froze more to the CS when it was presented outside of its extinction context, but froze equally in both contexts after muscimol infusion. In parallel with the behavior, lateral nucleus neurons exhibited context-dependent firing to extinguished CSs, and hippocampal inactivation disrupted this activity pattern. These data reveal a novel role for the hippocampus in regulating the context-specific firing of lateral amygdala neurons after fear memory extinction.

Post-training reversible inactivation of the hippocampus enhances novel object recognition memory

“…In this study, we inactivated the dorsal hippocampus using muscimol, a GABA receptor type A agonist that has been used previously to inhibit hippocampal activity (Moser and Moser 1998;Holt and Maren 1999;Maren and Hobin 2007). Muscimol was injected into the dorsal hippocampus through guide cannulae implanted in the mouse brain by stereotaxic surgery.…”

Changing Fear: The Neurocircuitry of Emotion Regulation

“…Another possibility is that the hippocampus gates fear expression directly through projections to the LA. A recent study showed that the context-specific modulation of both fear expression and CS-evoked activity in the LA (greater responding in the non-extinction context than in the extinction context) depends on the hippocampus (Maren and Hobin, 2007). Although clarification of the precise circuitry requires further investigation, there is strong evidence that the hippocampus, through communication with the vmPFC and the amygdala, regulates the contextual modulation of fear expression during extinction retrieval.…”

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

“…Frodl et al (2002) found reduced hippocampal volume in male participants with first-ever depressive episode, suggesting that hippocampal degeneration precedes the onset of depression. Structures, such as the prefrontal cortex, the amygdala, and nucleus accumbens receive inputs from the hippocampus, thus providing a possibility for altered hippocampal function to affect emotionality (Maren and Hobin 2007;O'Donnell and Grace 1995). A recent prospective study, however, disagrees with this theory, as they reported that depression might lead to a faster rate of hippocampal volume decline, but they found no evidence for smaller hippocampal volume to precede the development of depression (den Heijer et al 2011).…”