Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

Abstract

The habenula complex modulates the a ctivity of dopamine and serotonin systems in the brain. An important question remains whether there is a link between habenula dysfunction and monoaminerelated disorders, such as schizophrenia. In this study, we describe an interaction between habenula lesions and stress that produces long-lasting effects on behavior. Mice received control lesions or bilateral electrolytic lesions of the habenula and were tested for fear-potentiated startle and freezing measures of conditioned fear. They w ere also tested for prepulse inhibition (PPI) and locomotor activity in the presence or absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with mixed dopamine/serotonin antagonist properties (clozapine). There were no detectable effects of habenula lesions on fear conditioning and no effects on PPI in the absence o f stress. However, following conditioned fear stress, habenula-lesioned animals showed decreased PPI which normalized with clozapine. Lesioned animals also showed diminished activity at baseline, with hyperlocomotion following apomorphine. These data support the hypothesis that the habenula may be normally involved in stress-dependent regulation of monoamine systems.

Involvement of the lateral habenula in the regulation of generalized anxiety- and panic-related defensive responses in rats

“…The microinjection of this excitatory amino acid did not significantly interfere with animals' locomotion in the open-field either in groups of animals previously tested in the elevated T-maze or in naïve rats, which again excludes motor impairment as the critical factor accounting for the results obtained in the elevated T-maze. Although prior studies have implicated the LHb in stress-related phenomena (Lee and Huang, 1988;Thornton and Bradbury, 1989;Heldt and Ressler, 2006), to our knowledge this is the first direct evidence of the involvement of this brain area in the modulation of defensive behaviors and hence in fear and anxiety.…”

Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories

“…Note that mice frequently display an unconditioned inhibition of acoustic startle, so that %FPS can exhibit a non-zero baseline as seen in Figure 5a. 48,49 When the separate post-extinction tests (sessions 2-4) were analyzed together (Figure 5b), we found a significant group effect for LV-GFP vs LV-Cre on %FPS (F(1.25) = 6.0, P < 0.05).…”

Determining the function of zebrafish epithalamic asymmetry

“…Following habenular lesions, rats also respond prematurely in a spatial learning paradigm, suggesting that behaviour becomes more impulsive (LeCourtier & Kelly 2005). In some cognitive assays, the effect of habenular loss is enhanced if stress levels are increased (Thornton & Bradbury 1989;Heldt & Ressler 2006). There is also evidence that habenular neurons respond to retinal illumination and may serve to link circadian and motivational pathways in the brain (Zhao & Rusak 2005).…”

“…Recent work in mammals has uncovered an interesting link between the habenular region and control of the dopaminergic mesolimbic pathway that mediates fear, motivation and reward (Heldt & Ressler 2006;Morissette & Boye 2008). Specifically, the lateral habenula nucleus was found to provide inhibitory signals to dopaminergic neurons in the ventral midbrain (Matsumoto & Hikosaka 2007).…”