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Lateral habenular neurons projecting to reward-processing monoaminergic nuclei express hyperpolarization-activated cyclic nucleotid-gated cation channels.

Abstract：

:The lateral habenular complex (LHb) is a key signal integrator between limbic forebrain regions and monoaminergic hindbrain nuclei. Major projections of LHb neurons target the dopaminergic ventral tegmental area (VTA) and the serotonergic dorsal (DR) and median raphe nuclei (MnR). Both monoaminergic neurotransmitter systems play a central role in reward processing and reward-related decision-making. Glutamatergic LHb efferents terminate on GABAergic neurons in the VTA, the rostromedial tegmental nucleus (RMTg), and the raphe nuclei, thereby suppressing monoamine release when required by the present behavioral context. Recent studies suggest that the LHb exerts a strong tonic inhibition on monoamine release when no reward is to be obtained. It is yet unknown whether this inhibition is the result of a continuous external activation by other brain areas, or if it is intrinsically generated by LHb projection neurons. To analyze whether the tonic inhibition may be the result of a hyperpolarization-activated cyclic nucleotid-gated cation channel (HCN)-mediated pacemaker activity of LHb projection neurons, we combined retrograde tracing in rats with in situ hybridization of HCN1 to HCN4 mRNAs. In fact, close to all LHb neurons targeting VTA or raphe nuclei are equipped with HCN subunit mRNAs. While HCN1 mRNA is scarce, most neurons display strong expression of HCN2 to HCN4 mRNAs, in line with the potential formation of heteromeric channels. These results are supported by quantitative PCR and immunocytochemical analyses. Thus, our data suggest that the tonic inhibition of monoamine release is intrinsically generated in LHb projection neurons and that their activity may only be modulated by synaptic inputs to the LHb.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Poller WC,Bernard R,Derst C,Weiss T,Madai VI,Veh RW

doi

10.1016/j.neuroscience.2011.07.013

subject

Has Abstract

pub_date

2011-10-13 00:00:00

pages

205-16

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(11)00808-6

journal_volume

193

pub_type

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Lateral habenular neurons projecting to reward-processing monoaminergic nuclei express hyperpolarization-activated cyclic nucleotid-gated cation channels.