Physiological Evidence for Habenula as Major Link Between Forebrain and Midbrain Raphe

Wang, Rex Y.; Aghajanian, George K.

doi:10.1126/science.194312

Cited by 382 publications

(209 citation statements)

References 17 publications

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“…Moreover, no effect of serotonin depletion on increased premature responses provoked by low amphetamine doses was observed (Harrison et al, 1997). Regarding the habenula lesion effect, the majority of studies indicate an inhibitory influence of habenula activity on serotonergic neurons (Wang and Aghajanian, 1977;Speciale et al, 1980;Reisine et al, 1982), such that the effect of lesions would be elevated serotonin release, which would be predicted to decrease premature responding. In contrast to premature responding, choice accuracy was not significantly altered shortly after habenula lesion, but was impaired at later times.…”

Section: Discussionmentioning

confidence: 99%

Bilateral Lesions of the Habenula Induce Attentional Disturbances in Rats

Lecourtier

Kelly

2004

Neuropsychopharmacol

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The habenular nuclear complex is a major influence on brainstem cell groups that influence attention, but its role in attentional performance has not previously been explored. The present study investigated how habenula lesions affect attentional function as assessed by the 5-choice serial reaction time task (5-CSRTT) in male Lister-Hooded rats. Rats were pretrained in the 5-CSRTT before receiving discrete bilateral lesions of the habenula or a sham procedure. In test sessions immediately following recovery from surgery, lesioned rats showed a marked increase in premature responding. Over the course of testing this increase of premature responding declined in magnitude. In contrast, choice accuracy showed no impairment during the earliest postsurgery test sessions but progressively deteriorated over the course of testing. These opposite time courses strongly imply that different mechanisms mediate these two effects of the habenula lesion. Differential effects of drug treatment on these effects further supported this view. Thus, D-amphetamine (0.2 mg/ kg s.c.) increased premature responding without affecting choice accuracy. On the other hand, haloperidol (0.01-0.03 mg/kg i.p.) decreased premature responding without significantly affecting choice accuracy. The results are consistent with the view that elevated premature responding in habenula-lesioned animals is mediated by increased dopaminergic activity, whereas impaired choice accuracy is not. Implications of these findings for the hypothesis that habenula dysfunction is involved in cognitive symptoms of schizophrenia are discussed.

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Section: Discussionmentioning

confidence: 99%

Bilateral Lesions of the Habenula Induce Attentional Disturbances in Rats

Lecourtier

Kelly

2004

Neuropsychopharmacol

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“…For example, physiological studies (Stem et al, 1979;Wang and Aghajanian, 1977) and neurochemical measurements (Speciale et al, 1980) suggest that the habenula is a major link between forebrain structures and midbrain serotonin-containing neurons. The present study suggests that the habenula also serves as a link between forebrain structures and midbrain dopaminergic neurons.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat

Christoph¹,

Leonzio²,

Wilcox³

1986

J. Neurosci.

375

289

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Neurons in the lateral habenula (LHb) of rats have efferent projections that terminate in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), where cell bodies of dopamine-containing neurons are located. In order to study the influence of the habenula on dopaminergic activity, single-cell electrophysiological techniques were used to record unit discharge of dopamine-containing neurons in the SNC and VTA during electrical stimulation of the LHb or adjacent structures. Dopamine-containing neurons in the SNC and VTA were identified by their characteristic spike duration (>2 msec), discharge rate (2-8 spikes/set), and irregular firing pattern. Analysis of peristimulus time histograms showed that 85% of SNC cells and 91% of VTA neurons were inhibited after single pulse stimulation (0.25 mA, 0.1 msec) of the LHb. The mean time between stimulation and onset of inhibition was 11 msec (range, 2-22 msec) and mean duration of maximal suppression was 76 msec (range, 20-250 msec). Stimulation of structures adjacent to the LHb (hippocampus, lateral thalamus, medial dorsal thalamus, medial habenula) had little or no effect. Destruction of the fasciculus retroflexus, the fiber pathway that contains most habenular efferents, blocked the stimulation effects on dopamine-containing neurons. Destruction of the stria medullaris, which contains most habenular afferents, did not alter the inhibitory effect of habenular stimulation. Injection of a cytotoxin, kainic acid, in the LHb 1 week before recording sessions blocked the inhibitory consequences of habenular stimulation. These experiments show that activation of neuronal perikarya in the LHb causes orthodromic inhibition of dopamine-containing neurons in SNC and VTA via the fasciculus retroflexus.

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“…The habenula receives convergent input from most limbic brain regions including the hypothalamus, central amygdala, substantia innominata, diagonal band of Broca, nucleus accumbens, septum, and prefrontal cortical regions (Sutherland, 1982;Ellison, 2002). In addition to receiving afferent input from brainstem dopamine and serotonergic systems, it is a principle regulator of firing of the ventral tegmental area (VTA), dorsal raphe nucleus (DRN), and interpeduncular nucleus (IP) (Wang and Aghajanian, 1977;Reisine et al, 1982;Skagerberg et al, 1984;Nishikawa et al, 1986;Varga et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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

Heldt

Ressler

2006

Brain Research

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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.

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Physiological Evidence for Habenula as Major Link Between Forebrain and Midbrain Raphe

Cited by 382 publications

References 17 publications

Bilateral Lesions of the Habenula Induce Attentional Disturbances in Rats

Bilateral Lesions of the Habenula Induce Attentional Disturbances in Rats

Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat

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

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