title: Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin.
abstract: The lateral habenula (LHb) has recently been identified as a key regulator of the reward system by driving inhibition onto dopaminergic neurons. However, the nature and potential modulation of the major input to the LHb originating from the basal ganglia are poorly understood. Although the output of the basal ganglia is thought to be primarily inhibitory, here we show that transmission from the basal ganglia to the LHb is excitatory, glutamatergic, and suppressed by serotonin. Behaviorally, activation of this pathway is aversive, consistent with its role as an "antireward" signal. Our demonstration of an excitatory projection from the basal ganglia to the LHb explains how LHb-projecting basal ganglia neurons can have similar encoding properties as LHb neurons themselves. Our results also provide a link between antireward excitatory synapses and serotonin, a neuromodulator implicated in depression.
authors.affiliation: Center for Neural Circuits and Behavior, Division of Biology, Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Shabel
authors.forename: Christophe D
authors.initials: CD
authors.lastname: Proulx
authors.forename: Anthony
authors.initials: A
authors.lastname: Trias
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Murphy
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology*; D001479:Basal Ganglia / Q000502:physiology*; D001703:Biophysics; D000075402:Channelrhodopsins; D002772:Cholera Toxin / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D019262:Habenula / Q000166:cytology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D055095:Optics and Photonics; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011810:Quinoxalines; D050599:Vesicular Glutamate Transport Protein 2; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D012701:Serotonin; D002772:Cholera Toxin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D004298:Dopamine