Basolateral Amygdala Inputs to the Medial Entorhinal Cortex Selectively Modulate the Consolidation of Spatial and Contextual Learning

Abstract

Although evidence suggests that the basolateral amygdala (BLA) and dorsal hippocampus (DH) work together to influence the consolidation of spatial/contextual learning, the circuit mechanism by which the BLA selectively modulates spatial/contextual memory consolidation is not clear. The medial entorhinal cortex (mEC) is a critical region in the hippocampus-based system for processing spatial information. As an efferent target of the BLA, the mEC is a candidate by which the BLA influences the consolidation of such learning. To address several questions regarding this issue, male Sprague Dawley rats received optogenetic manipulations of different BLA afferents immediately after training in different learning tasks. Optogenetic stimulation of the BLA-mEC pathway using ChR2(E123A) after spatial and cued-response Barnes maze training enhanced and impaired retention, respectively, whereas optical inhibition of the pathway using eNpHR3.0 produced trends in the opposite direction. Similar stimulation of the BLA-posterior dorsal striatum pathway had no effect. BLA-mEC stimulation also selectively enhanced retention for the contextual, but not foot shock, component of a modified contextual fear-conditioning procedure. In both sets of experiments, only stimulation using bursts of 8 Hz light pulses significantly enhanced retention, suggesting the importance of driving activity in this frequency range. An 8 Hz stimulation of the BLA-mEC pathway increased local field potential power in the same frequency range in the mEC and in the DH. Together, the present findings suggest that the BLA modulates the consolidation of spatial/contextual memory via projections to the mEC and that activity within the 8 Hz range is critical for this modulation. The mechanism by which the basolateral amygdala (BLA) influences the consolidation of spatial/contextual memory is unknown. Using an optogenetic approach with multiple behavioral procedures, we found that immediate posttraining 8 Hz stimulation of BLA projections to the medial entorhinal cortex (mEC) enhanced retention for spatial/contextual memory, impaired retention for cued-response memory, and had no effect on foot shock learning for contextual fear conditioning. Electrophysiological recordings confirmed that 8 Hz stimulation of this pathway increased activity in the 8 Hz range in the mEC and in the dorsal hippocampus, a region critical for spatial memory consolidation. This suggests that coordinated BLA activity with downstream regions in the 8 Hz activity range immediately after training is important for consolidation of multiple memory forms.

Optogenetic Stimulation of the Basolateral Amygdala Increased Theta-Modulated Gamma Oscillations in the Hippocampus

“…For example, activation of the amygdala is thought to facilitate information transfer from the perirhinal cortex to the entorhinal cortex, which in turn would influence the input to the hippocampus (Kajiwara et al, 2003; Paz et al, 2006). In addition, stimulation of the BLA-entorhinal cortex pathway was previously found to enhance hippocampal-dependent memories (Wahlstrom et al, 2018). Additional support for the importance of this perirhinal-entorhinal pathway comes from past studies showing that BLA stimulation modulated hippocampal LTP in the dentate gyrus (Abe, 2001; Akirav and Richter-Levin, 2002; Vouimba and Richter-Levin, 2005), which receives input from the entorhinal cortex but not from the BLA (Pitkänen et al, 2000; Witter and Amaral, 2004).…”

Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

“…Interestingly, both PREG, which is metabolized to ALLO, and PregS, which is a positive modulator of NMDARs, improve working memory function in patients with schizophrenia in which cortical disinhibition due to hypofunction of excitatory NMDARs on PV interneurons in the prefrontal cortex has been implicated (51, 52, 65, 237, 238). Parahippocampal and hippocampal structures including, the trisynaptic circuit receives sensory and emotional inputs from sensory modalities via the thalamus (shown in orange) and the amygdala, respectively (396–398). The impact of powerful emotion-evoking stimuli are state independent when ALLO is injected into the amygdala and hippocampus, but state-dependent when it is injected into the BNST (shown in gray) (246).…”

High-fat diet worsens the impact of aging on microglial function and morphology in a region-specific manner

“…It is well known that inactivating the amygdala (via neurotoxic lesions or pharmacological manipulations) interferes with consolidation of both contextual and cued fear memories, whereas inactivating the hippocampus interferes with consolidation of contextual but not cued fear memory (Antoniadis & McDonald, 2000;Phillips & LeDoux, 1992). It has been further demonstrated that the basolateral amygdala plays a critical role, in conjunction with the hippocampus, to modulate consolidation of contextual memories (Huff & Rudy, 2004), and it does so through inputs to the medial entorhinal cortex (Wahlstrom et al, 2018). It is therefore very possible that the microglial changes observed here in the amygdala are driving the memory deficits we have previously reported (Spencer et al, 2017).…”