GABAergic mechanisms of anterior and ventromedial hypothalamic nuclei in the expression of freezing in response to a light-conditioned stimulus.

Julia Maria Dos Santos,Marcus Lira Brandão

doi:10.3922/j.psns.2011.2.006

Abstract

The amygdala, dorsal periaqueductal gray (dPAG), and medial hypothalamus have long been recognized to comprise a neural system responsible for the generation and elaboration of unconditioned fear in the brain. This neural substrate is well known to be under tonic inhibitory control exerted by γ-aminobutyric acid (GABA) mechanisms. Some evidence also suggests that these structures integrate conditioned fear. A recent study using the fear-potentiated startle paradigm showed that GABAergic mechanisms in the anterior hypothalamic nucleus (AHN) and dorsomedial part of the ventromedial hypothalamic nucleus (VMHDM) regulate conditioned fear. The present study examined the extent to which GABAergic mechanisms in these brain regions are involved in conditioned fear by measuring freezing in response to a light used as a conditioned stimulus (CS). The GABAA receptor agonist muscimol and the GABA-synthesizing enzyme glutamic acid decarboxylase inhibitor semicarbazide were used as an enhancer and inhibitor of GABA mechanisms, respectively. Muscimol and semicarbazide were injected into the AHN or VMHDM of rats before fear conditioning. Muscimol injections into the AHN and VMHDM significantly reduced conditioned freezing, whereas inhibition of GABA transmission increased this conditioned response in the AHN. The present study further supports the hypothesis that GABAergic mechanisms in the AHN and VMHDM exert inhibitory control on the neural substrates of conditioned fear in the hypothalamus.

Highlights

The medial hypothalamus, amygdala, and dorsal periaqueductal gray have long been recognized to comprise a neural system responsible for the generation and elaboration of aversive states in the brain (Brandão, Anseloni, Pandóssio, De Araújo, & Castilho, 1999; Graeff, 2004)
Post hoc comparisons indicated that muscimol inhibited conditioned freezing in response to the light conditioned stimulus (CS) (p < 0.05)
The circuit formed by the anterior hypothalamic nucleus (AHN), dorsomedial hypothalamus (DMH), VMHDM, and PMD comprises regions mainly activated by predatory encounters, supporting the existence of a segregated subsystem in the medial zone of the hypothalamus involved in the expression of innate fear responses (Canteras et al, 1997; Canteras, 2002)

Summary

Introduction

The medial hypothalamus, amygdala, and dorsal periaqueductal gray (dPAG) have long been recognized to comprise a neural system responsible for the generation and elaboration of aversive states in the brain (Brandão, Anseloni, Pandóssio, De Araújo, & Castilho, 1999; Graeff, 2004). Interesting for the present study is that the medial zone of the hypothalamus contains diverse, well-defined These sites include a circuit formed by the anterior hypothalamic nucleus (AHN), dorsomedial portion of the ventromedial nucleus of the hypothalamus (VMHDM), dorsomedial hypothalamus (DMH), and dorsal premammillary nucleus (PMD), which has been termed the defensive hypothalamic area. This circuit is hypothesized to integrate innate defensive responses primarily involved in the processing of predatory threats (Canteras, 2002; Canteras et al 1997; Johnson & Shekhar, 2006). The AHN and PMD, but not VMHDM, appear to be involved in contextual conditioning to predator cues

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