Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression

Meng, Hongmei; Wang, Yanan; Huang, Min; Lin, Weihong; Shao, Wei; Bai-min, Zhang

doi:10.1016/j.brainres.2011.08.041

Cited by 100 publications

(58 citation statements)

References 29 publications

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“…Ventral tegmental area stimulation in Flinders rats increased sucrose self-administration, improved social interaction, and increased exploratory behavior in a novelty suppressed feeding test (31). In the open field, both NAc and LHb stimulation increased exploratory behavior in naïve and Kyoto Wistar rats (28,30).…”

Section: Dbs Effects In Other Animal Modelsmentioning

confidence: 99%

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Preclinical Studies Modeling Deep Brain Stimulation for Depression

Hamani¹,

Nóbrega²

2012

Biological Psychiatry

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Deep brain stimulation (DBS) is currently being investigated for the treatment of depression. Results of early clinical trials have been very promising, but the mechanisms responsible for the effects of DBS are still unknown. This article reviews behavioral findings of stimulation applied to different brain targets in rodents, with a particular focus on the ventromedial prefrontal cortex. Mechanisms and substrates involved in the antidepressant-like effects of DBS, including the role of local tissue inactivation, the modulation of fiber pathways in the vicinity of the electrodes, as well as the importance of the serotonergic system and brain derived neurotrophic factor are discussed. KeywordsAnimal models; deep brain stimulation; depression; fiber pathways; psychiatry; radiofrequency lesions; serotonin Deep brain stimulation (DBS) has been investigated for the treatment of depression with promising clinical results (1-11). Although preclinical research using electrical stimulation to study behavior has been conducted for over 50 years, results from animal studies did not comprise the rationale for the current use of DBS in depression. Experiments i n animal models to investigate substrates and mechanisms responsible for the antidepressant-like effects of DBS were only conducted after the initial clinical trials were published (2,7,8,(10)(11)(12).This article provides an overview of current findings and some of the emerging concepts from experiments with DBS in models of depression, with a particular focus on results obtained with ventromedial prefrontal cortex (vmPFC) stimulation in rodents. CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscript Choosing a Stimulation TargetThe medial surface of the frontal cortex in rodents has been subdivided into four cytoarchitectural regions: the agranular frontal cortex, anterior cingulate cortex (AC), prelimbic cortex (PL), and infralimbic cortex(IL)( Figure 1A)(13-15).Alternatively, it has also been subdivided into dorsal and ventral "systems," according to functional role as well as afferent and efferent projections (15). The dorsal system includes the frontal agranular cortex, AC, and dorsal PL and seems to be involved in the control of eye and head movements (14-16). The ventral system, comprises the IL and ventral aspects of the PL (vPL), projects mainly to the amygdala, hypothalamus, insula, and brainstem and has been suggested to play a role in autonomic control (17)(18)(19)(20). Vertes (21) proposed an alternative subdivision of the medial prefrontal cortex (PFC) in dorsal (frontal agranular cortex and AC) and ventral regions (PL and IL). To mimic the effects of subgenual cingulum (SCG) DBS in rodents, we have been applying stimulation to the vmPFC (12,(22)(23)(24)(25)(26), including IL and vPL.Overall, the limits of the vPL are hard to delineate. However, if an arbitrary line is traced dividing the PL into dorsal and ventral halves, the approximate anteroposterior, mediolateral, and dorsoventral dimensions of the vmPFC (including IL and vPL...

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Section: Dbs Effects In Other Animal Modelsmentioning

confidence: 99%

“…In addition to the vmPFC, targets recently studied in animal models include the nucleus accumbens (NAc) (28,29), lateral habenula (LHb) (30), and ventral tegmental area (VTA) (31).…”

mentioning

confidence: 99%

Preclinical Studies Modeling Deep Brain Stimulation for Depression

Hamani¹,

Nóbrega²

2012

Biological Psychiatry

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“…Velike depresivne epizode karakterišu epizode depresivnog raspoloženja, uz smanjenje motivacije za ostvarivanjem hedonističkih ciljeva (42). Smatra se posledicom poremećene regulacije neurotransmisije monoamina, odnosno dopamina, serotonina i norepinefrina, dok se poboljšanje postiže povećanjem i normalizovanjem nivoa ovih neurotransmitera u mozgu (41).…”

Section: Kontrola Sistema Zadovoljstva I Motornog Odgovoraunclassified

“…Međutim, 20-30% pacijenata obolelih od depresije rezistentno je na standardnu terapiju koja obuhvata antidepresive, psihoterapiju i elektrokonvulziju (63 stimulacija, koja se postiže stereotaksičkim postavljanjem elektroda, pokazala se kao bezbedna i efikasna metoda u lečenju pacijenata sa Parkinsonovom bolešću, esencijalnim tremorom, distonijom, klaster glavoboljama i hroničnim bolnim stanjima (64)(65)(66)(67), kao i u lečenju depresije (68). Ciljna područja za primenu duboke moždane stimulacije u lečenju depresije kod pacijenta rezistentnih na terapiju predložena su na osnovu istraživanja i uključuju lateralno jedro habenule (44,68), prednji krak capsulae internae nucleus accumbens (Nac) i pedunculi thalami (41). duboka moždana stimulacija habenule, postavljanjem elektroda u stria medullaris, glavni limbički aferentni snop habenule, rezultirala je otklanjanjem simptoma depresije, odnosno remisijom kod pacijenata rezistentnih na sve ostale oblike terapije (69).…”

Section: Kontrola Sistema Zadovoljstva I Motornog Odgovoraunclassified

“…Potvrđena je funkcionalna modulacija striae medullaris, kao i porast koncentracije norepinefrina u hipokampusu i medijalnom prefrontalnom korteksu, kao i serotonina u striatumu (70)(71)(72). Pretpostavlja se da visokofrekventna duboka moždana stimulacija povećava oslobađanje inhibitornih neurotransmitera iz presinaptičkih neurona (73), što smanjuje aktivnost jedara habenule i njihov inhibitorni uticaj na monoaminergičke neurone (41). Pokazano je i da na taj način smanjena aktivnost lateralne habenule povećava serumsku koncentraciju moždanog neurotrofnog faktora (BdNF), koja se povećava i posle primene antidepresiva (74).…”

Section: Kontrola Sistema Zadovoljstva I Motornog Odgovoraunclassified

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10.5937/mckg48-5899 = Functional and anatomical aspects of the habenular complex of epithalamus

Marković¹,

Ognjanović²

2014

Medicinski casopis

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UVODepitalamus (epithalamus) predstavlja deo međumozga, smešten na dorzokaudalnom delu talamusa i po svojoj anatomskoj poziciji, ali i neuronskim vezama predstavlja "raskrsnicu" na kojoj se ukrštaju putevi limbičkog sistema, bazalnih ganglija, ali i mnogi drugi neuronski krugovi. Morfološki gledano sastoji se iz epifize (gl. pinealis), habenularnih jedara (nuclei habenulae), međuhabenularne spojnice (commisura habenularum) i striae medularis. Habenularni kompleks je parna struktura epitalamusa, sastavljena iz dva jedra -medijalnog (nc. habenularis medialis -MHb) i lateralnog (nc. habenularis lateralis -lHb). to je filogenetski stara moždana struktura sa kod većine kičmenjaka jasno uočljivom asimetrijom u veličini kompleksa desne i leve strane (1). Medijalno jedro habenule izgrađeno je od gusto pakovanih nervnih ćelija koje su na osnovu svojih citoarhitektonskih karakteristika svrstane u pet subnukleusa (2), dok se u okviru lateralnog habenularnog jedra opisuje 10 subnukleusa (3). anatomska lokalizacija i veze omogućavaju jedrima habenule ulogu u regulaciji mnoštva fizioloških mehanizama, ali i u patogenezi pojedinih bolesti, kao što su depresija, shizofrenija, Parkinsonova bolest, bolesti zavisnosti i dr. (4). u ovom radu prikazuju se nova saznanja o ulozi habenularnog kompleksa u normalnim, fiziološkim procesima, kao i patogenezi psihijatrijskih oboljenja. NEURONSKE VEZE HABENULARNOG KOMPLEKSAHabenularni kompleks predstavlja glavnu vezu između bazalnih ganglija i limbičkih delova telencefalona, s jedne

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Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat

Sego

Gonçalves

Lima

et al. 2014

J of Comparative Neurology

102

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The lateral habenula (LHb) is an epithalamic structure differentiated in a medial (LHbM) and a lateral division (LHbL). Together with the rostromedial tegmental nucleus (RMTg), the LHb has been implicated in the processing of aversive stimuli and inhibitory control of monoamine nuclei. The inhibitory LHb influence on midbrain dopamine neurons has been shown to be mainly mediated by the RMTg, a mostly GABAergic nucleus that receives a dominant input from the LHbL. Interestingly, the RMTg also projects to the dorsal raphe nucleus (DR), which also receives direct LHb projections. To compare the organization and transmitter phenotype of LHb projections to the DR, direct and indirect via the RMTg, we first placed injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the LHb or the RMTg. We then confirmed our findings by retrograde tracing and investigated a possible GABAergic phenotype of DR-projecting RMTg neurons by combining retrograde tracing with in situ hybridization for GAD67. We found only moderate direct LHb projections to the DR, which mainly emerged from the LHbM and were predominantly directed to the serotonin-rich caudal DR. In contrast, RMTg projections to the DR were more robust, emerged from RMTg neurons enriched in GAD67 mRNA, and were focally directed to a distinctive DR subdivision immunohistochemically characterized as poor in serotonin and enriched in presumptive glutamatergic neurons. Thus, besides its well-acknowledged role as a GABAergic control center for the ventral tegmental area (VTA)-nigra complex, our findings indicate that the RMTg is also a major GABAergic relay between the LHb and the DR.

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Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression

Cited by 100 publications

References 29 publications

Preclinical Studies Modeling Deep Brain Stimulation for Depression

Preclinical Studies Modeling Deep Brain Stimulation for Depression

10.5937/mckg48-5899 = Functional and anatomical aspects of the habenular complex of epithalamus

Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat

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