Amygdalar Stimulation Produces Alterations on Firing Properties of Hippocampal Place Cells

Abstract

Stress is a biologically ubiquitous factor that, when perceived uncontrollable by humans and animals, can have lingering adverse effects on brain and cognitive functions. We have previously reported that rats that experienced inescapable-unpredictable stress subsequently exhibited decreased stability of firing rates of place cells in the CA1 hippocampus, accompanied by impairments in CA1 long-term synaptic potentiation and spatial memory consolidation. Because the elevated level of glucocorticoid hormones and the heightened amygdalar activity have been implicated in the emergence of stress effects on the hippocampus, we investigated whether administration of corticosterone and electrical stimulation of the amygdala can produce stress-like alterations on hippocampal place cells. To do so, male Long-Evans rats chronically implanted with tetrodes in the hippocampus and stimulating electrodes in the amygdala were placed on a novel arena to forage for randomly dispersed food pellets while CA1 place cells were monitored across two recording sessions. Between sessions, animals received either corticosterone injection or amygdalar stimulation. We found that amygdalar stimulation reliably evoked distress behaviors and subsequently reduced the pixel-by-pixel correlation of place maps across sessions while corticosterone administration did not. Also, the firing rates of place cells between pre- and post-amygdalar stimulation recording sessions were pronouncedly different whereas those between pre- and post-corticosterone injection recording sessions were not. These results suggest that the heightened amygdalar activity, but not the elevated level of corticosterone per se, reduces the stability of spatial representation in the hippocampus by altering the firing rates of place cells in a manner similar to behavioral stress.

Alterations of Hippocampal Place Cells in Foraging Rats Facing a “Predatory” Threat

“…The stress hormones (e.g., glucocorticoids), released by the hypothalamic-pituitary-adrenal axis and implicated in mediating stress effects on the hippocampus [33, 34], are too slow in temporal (rise-fall) dynamics to account for the present distal-proximal differences in place fields and theta rhythm (see also [35]). An alternative possibility is the nature of interaction between the hippocampus processing spatial (cognitive) information and the amygdala processing fear (emotional) information [36], which is essential for animals to make optimal decisions in risky situations.…”

“…Consistent with this notion, amygdala-lesioned rats showed no overt fear behavior to the robot and their place fields in the vicinity of the robot were just as stable as those inside/near the nest. Other lines of evidence also indicate an amygdala-hippocampus interaction, such as: (i) a previously fear conditioned tone stimulus inducing place cell remapping which was blocked by inactivating the amygdala [37], (ii) fear-conditioned stimuli and stress increasing theta synchrony between the amygdala and hippocampus [38–40], (iii) amygdala stimulation decreasing ensuing CA1 long-term potentiation (LTP) [41] and reducing the stability of place fields in CA1 place cells [35], and (iv) amygdala lesions blocking stress-induced alterations of CA1 LTP and spatial memory [42]. To elucidate the nature of the amygdala-hippocampus interaction, future studies will need to determine whether the activity of fear encoding neurons in the amygdala scales the foraging distance and correlates with place cell remapping, and whether optogenetic silencing (and stimulating) amygdalar neurons prevents (and causes) the remapping of distal (and proximal) place fields.…”

Amygdala-mediated enhancement of memory for specific events depends on the hippocampus

“…There are direct and indirect connections between the BLA and the hippocampus (Petrovich et al, 2001; Pitkanen et al, 2000), and BLA stimulation can modulate plasticity in cortical areas outside the hippocampus (Chavez, McGaugh, & Weinberger, 2009; Paz, Pelletier, Bauer, & Pare, 2006) as well as in the hippocampus (Akirav & Richter-Levin, 1999; Frey et al, 2001; Ikegaya et al, 1995; Kim, Kim, Park, Cho, & Kim, 2012; McIntyre et al, 2005). A common view is that BLA activation affects signaling cascades related to late-phase LTP in numerous brain regions in support of memory consolidation (Bergado, Lucas, & Richter-Levin, 2011; McGaugh, 2004; Pare, 2003).…”

Stress effects on the hippocampus: a critical review

“…It should be mentioned that amygdalar lesions/inactivation blocked stress effects on hippocampal LTP and memory despite the increase in CORT levels (see also Shors et al 1989). Recently, electrical stimulation of the amygdala was found to be sufficient in suppressing CA1 LTP (Vouimba and Richter-Levin 2005) and altering place cell activity (Kim et al 2012). These findings suggest that the amygdala is a critical component of the central stress mechanism affecting hippocampal functioning.…”