Afferent and efferent connections of the interpeduncular nucleus with special reference to circuits involving the habenula and raphe nuclei

Abstract

The habenula is an epithalamic structure differentiated into two nuclear complexes, medial (MHb) and lateral habenula (LHb). Recently, MHb together with its primary target, the interpeduncular nucleus (IP), have been identified as major players in mediating the aversive effects of nicotine. However, structures downstream of the MHb-IP axis, including the median (MnR) and caudal dorsal raphe nucleus (DRC), may contribute to the behavioral effects of nicotine. The afferent and efferent connections of the IP have hitherto not been systematically investigated with sensitive tracers. Thus, we placed injections of retrograde or anterograde tracers into different IP subdivisions or the MnR and additionally examined the transmitter phenotype of major IP and MnR afferents by combining retrograde tract tracing with immunofluorescence and in situ hybridization techniques. Besides receiving inputs from MHb and also LHb, we found that IP is reciprocally interconnected mainly with midline structures, including the MnR/DRC, nucleus incertus, supramammillary nucleus, septum, and laterodorsal tegmental nucleus. The bidirectional connections between IP and MnR proved to be primarily GABAergic. Regarding a possible topography of IP outputs, all IP subnuclei gave rise to descending projections, whereas major ascending projections, including focal projections to ventral hippocampus, ventrolateral septum, and LHb originated from the dorsocaudal IP. Our findings indicate that IP is closely associated to a distributed network of midline structures that modulate hippocampal theta activity and forms a node linking MHb and LHb with this network, and the hippocampus. Moreover, they support a cardinal role of GABAergic IP/MnR interconnections in the behavioral response to nicotine.

Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

“…In addition, mPOA MCH neurones did not colocalise with VGLUT2 cell bodies, a well‐established marker of glutamatergic neurones in the hypothalamus (Figure B). VGLUT3‐expressing cell bodies can be observed in several brain regions, particularly in the brainstem . In the preoptic area, VGLUT3 expression was basically restricted to axon terminals, many of them making apparent contacts with MCH neurones (Figure C).…”

“…VGLUT1 was not studied because this transporter is poorly expressed in the hypothalamus; however, we cannot rule out the possibilty that VGLUT1 mediates glutamate release in mPOA MCH neurones. Additionally, VGLUT3 antibody labels predominantly synaptic terminals in the hypothalamus, although cell bodies can be observed in the paraventricular nucleus of the hypothalamus (J. Donato, unpublished data) and in the brainstem …”

“…VGLUT3-expressing cell bodies can be observed in several brain regions, particularly in the brainstem. 50,51 In the preoptic area, VGLUT3 expression was basically restricted to axon terminals, many of them making apparent contacts with MCH neurones ( Figure 2C). Despite these apparent synaptic contacts, very few VGLUT3-expressing cell bodies colocalised with MCH neurones in the preoptic area (Table 1).…”

Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving

“…However, insofar as MHb fibers pass through LHb enroute to the fr and passing axons and terminal fields are poorly differentiated by anterograde tracing with audioradiography, the question had remained open. Recently, however, Lima et al (2017) have provided tracing evidence for reciprocal connections between MHb and LHbM (but see Kim and Chang, 2005). Similarly, Kim (2009) has demonstrated convincingly with complementary retrograde and anterograde tract tracing that homologous parts of the LHb on the two sides of the midline are robustly related by reciprocal connections.…”

Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior

“…More specifically, the MHb may play a larger role in adaptive behaviors, where mounting evidence has demonstrated that loss of vMHb function leads to deficits in fear extinction and escape behaviors. Nevertheless, while the circuitry and cellular composition of the MHb has been well-characterized, the endogenous functions of the MHb remain relatively unknown and have recently become the focus of addiction neuroscience (Qin & Luo 2009;Aizawa et al 2012;Lima et al 2017).…”