Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations.

Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated. We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation. Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala. These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867.

Flores Á ，Herry C ，Maldonado R ，Berrendero F ... -  《-》

The hypocretin/orexin system mediates the extinction of fear memories.

Flores Á ，Valls-Comamala V ，Costa G ，Saravia R ，Maldonado R ，Berrendero F ... -  《-》

Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala.

Kim WB ，Cho JH 《-》

Investigating the role of the amygdala orexin receptor 1 in memory acquisition and extinction in a rat model of PTSD.

Understanding the mechanisms underlying memory is essential for the treatment of post-traumatic stress disorder (PTSD). Orexin, as a lateral hypothalamic (LH) neuropeptide, interferes with the stages of memory, primarily through the orexin receptor1 (Orx1R). The aim of this study was to evaluate the effects of amygdala Orx1R in the acquisition and extinction processes of PTSD modeled in animals. In three experiments, rats were divided into three groups: control (Naïve), shock (receiving a foot shock), and PTSD (experiencing Single prolonged stress (SPS) method). The first experiment aimed to evaluate LH activity in PTSD modeled rats. The second and third experiments aimed to evaluate the effects of Orx1R in the acquisition and extinction of fear memory in PTSD modeled animals. SB334867 (SB) or its solvent was microinjected into the amygdala and the rats were subjected to conditioning thereafter. In the second group, we used a single injection after conditioning. In the third group, we used three consecutive injections (one after each memory test). Some behaviors and Orx1R expression were evaluated. The freezing response was significantly longer in the PTSD group than on the control. Similarly, anxiety and sensitized fear were also intensified. CFos expression levels in LH was higher in the PTSD group. Inhibition of Orx1R in the amygdala significantly decreased memory acquisition, diminished anxiety, and decreased the sensitized fear in the SB group. Applying SB to the amygdala after each fear memory test significantly decreased freezing. Expression of Orx1R was significantly higher following fear conditioning. These results indicate a likely involvement of the orexin and amygdalar Orx1R in memory acquisition and in extinction of PTSD.

Salehabadi S ，Abrari K ，Elahdadi Salmani M ，Nasiri M ，Lashkarbolouki T ... -  《-》

The basolateral amygdala orexin 1 and 2 receptors' involvement in modulating spatial reference memory.

Ardeshiri MR ，Hosseinmardi N ，Akbari E 《-》