The Synchronous Activity of Lateral Habenular Neurons Is Essential for Regulating Hippocampal Theta Oscillation

Abstract

Lateral habenula (LHb) has attracted growing interest as a regulator of serotonergic and dopaminergic neurons in the CNS. However, it remains unclear how the LHb modulates brain states in animals. To identify the neural substrates that are under the influence of LHb regulation, we examined the effects of rat LHb lesions on the hippocampal oscillatory activity associated with the transition of brain states. Our results showed that the LHb lesion shortened the theta activity duration both in anesthetized and sleeping rats. Furthermore, this inhibitory effect of LHb lesion on theta maintenance depended upon an intact serotonergic median raphe, suggesting that LHb activity plays an essential role in maintaining hippocampal theta oscillation via the serotonergic raphe. Multiunit recording of sleeping rats further revealed that firing of LHb neurons showed significant phase-locking activity at each theta oscillation cycle in the hippocampus. LHb neurons showing activity that was coordinated with that of the hippocampal theta were localized in the medial LHb division, which receives afferents from the diagonal band of Broca (DBB), a pacemaker region for the hippocampal theta oscillation. Thus, our findings indicate that the DBB may pace not only the hippocampus, but also the LHb, during rapid eye movement sleep. Since serotonin is known to negatively regulate theta oscillation in the hippocampus, phase-locking activity of the LHb neurons may act, under the influence of the DBB, to maintain the hippocampal theta oscillation by modulating the activity of serotonergic neurons.

Excitatory Transmission to the Lateral Habenula Is Critical for Encoding and Retrieval of Spatial Memory

“…Memory formation and retrieval depend upon the HPC (D'Hooge and De Deyn, 2001), and more specifically upon the presence of theta oscillations within the dHPC (Düzel et al, 2010). A high degree of synchrony between LHb and dHPC theta oscillations has recently been demonstrated (Aizawa et al, 2013b;Goutagny et al, 2013). Moreover, we have shown that spatial memory performance was positively correlated with theta coherence between the LHb and the dHPC (Goutagny et al, 2013).…”

“…We have shown that electrolytic habenular lesion altered hippocampus (HPC)-dependent spatial learning in the water maze (WM) (Lecourtier et al, 2004), whereas selective LHb inactivation induced memory deficits in an object-based, HPC-dependent memory task (Goutagny et al, 2013). Moreover, a high synchrony between LHb and dorsal HPC (dHPC) theta oscillations has been evidenced (Aizawa et al, 2013b;Goutagny et al, 2013). On the basis of the well-accepted view that communication between regions involves coherence of their oscillations (Fries, 2005), these data suggest that the LHb and dHPC are functionally connected and are likely to exchange information.…”

The role of lateral habenula–dorsal raphe nucleus circuits in higher brain functions and psychiatric illness

“…Another study reported that LHb lesions reduced the duration of REM sleep, an effect that depended on the activity of serotonergic neurons in the median raphe nucleus (MRN) [83]. Serotonin is known to play a critical role in the regulation of REM sleep by preventing pontine cholinergic systems from triggering REM onset [84].…”

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

“…Nedavna istraživanja potvrdila su pretpostavke da patološki izmenjena aktivnost neurona lHb utiče na razvoj simptoma depresije, kao što su pad raspoloženja (43,44), nemogućnost uživanja (45) i poremećaj sna (46). Smatra se da stresna stanja povećavaju nivo bazalne aktivnosti neurona lHb, što dovodi do kontinuirane inhibicije aktivnosti dopaminergičkih neurona mezencefalona i posledično, do smanjenja motorne aktivosti i motivacije (27,47), kao i do inhibicije serotinergičkih neurona nc.…”