Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala
S Berretta1, H Pantazopoulos, M Caldera
1Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA. s.berretta@mclean.harvard.edu
Insights
The infralimbic cortex excites intercalated neurons, which may inhibit fear responses. This study identifies a key pathway in fear extinction, revealing how the infralimbic cortex influences central amygdala activity.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Neurobiology
Background:
- The infralimbic cortex (IL) is crucial for conditioned fear extinction.
- IL stimulation inhibits central amygdala (CeA) neurons, the output of the amygdala for fear responses.
- The specific neurons mediating IL-induced CeA inhibition are unknown.
Purpose of the Study:
- To investigate whether the infralimbic cortex affects the activity of intercalated amygdala (ITC) neurons.
- To determine if IL activation leads to the inhibition of CeA neurons through ITCs.
Main Methods:
- Adult rats underwent local infusion of picrotoxin to disinhibit the IL.
- Neuronal activation was assessed by measuring Fos-immunoreactivity within the amygdala.
- Fos expression was quantified in the ITC, CeA, and basolateral amygdaloid complex (BLA).
Main Results:
- Disinhibition of the IL significantly increased Fos-immunoreactive ITC neurons bilaterally.
- No significant change in Fos expression was observed in the CeA.
- A significant increase in Fos-immunoreactive cells was found in the contralateral lateral nucleus of the BLA.
Conclusions:
- Glutamatergic inputs from the IL directly activate ITC neurons.
- The IL may inhibit conditioned fear by exciting ITCs, which then inhibit CeA neurons.
- This pathway provides a potential mechanism for fear extinction mediated by the IL.
Abstract:
Recently, it was reported that stimulation of the infralimbic cortex produces a feedforward inhibition of central amygdala neurons. The interest of this observation comes from the fact that the central nucleus is the main output station of the amygdala for conditioned fear responses and evidence that the infralimbic cortex plays a critical role in the extinction of conditioned fear. However, the identity of the neurons mediating this infralimbic-evoked inhibition of the central nucleus remains unknown. Likely candidates are intercalated amygdala neurons. Indeed, these cells receive glutamatergic afferents from the infralimbic cortex, use GABA as a transmitter, and project to the central amygdala. Thus, the present study was undertaken to test whether, in adult rats, the infralimbic cortex can affect the activity of intercalated neurons. To this end, disinhibition of the infralimbic cortex was induced by local infusion of the non-competitive GABA-A receptor antagonist picrotoxin. Subsequently, neuronal activation was determined bilaterally within the amygdala using induction of the immediate early gene Fos. Infralimbic disinhibition produced a significant increase in the number of Fos-immunoreactive intercalated cells bilaterally whereas no change was detected in the central nucleus. In the basolateral amygdaloid complex, increases in the number of Fos-immunoreactive cells only reached significance in the contralateral lateral nucleus. These results suggest that glutamatergic inputs from the infralimbic cortex directly activate intercalated neurons. Thus, our findings raise the possibility that the infralimbic cortex inhibits conditioned fear via the excitation of intercalated cells and the consequent inhibition of central amygdala neurons.
