The dorsal diencephalic conduction system in reward processing: Spotlight on the anatomy and functions of the habenular complex

HighlightsThe habenula is an epithalamic structure of the DDC linking forebrain to midbrain regions.The habenula regulates monoaminergic systems including those for dopamine and serotonin.Lateral habenula neurons encode negative reward prediction error and aversive stimuli.Sites within the DDC support operant responding for brain stimulation reward.Optogenetic activation of LHb projections to the midbrain produces behavioral avoidance. Abstract The dorsal diencephalic conduction system (DDC) is a highly conserved pathway in vertebrates that provides a route for the neural information to flow from forebrain to midbrain structures. It contains the bilaterally paired habenular nuclei along with two fiber tracts, the stria medullaris and the fasciculus retroflexus. The habenula is the principal player in mediating the dialogue between forebrain and midbrain regions, and functional abnormalities in this structure have often been attributed to pathologies like mood disorders and substance use disorder. Following Matsumoto and Hikosaka seminal work on the lateral habenula as a source of negative reward signals, the last decade has witnessed a great surge of interest in the role of the DDC in reward‐related processes. However, despite significant progress in research, much work remains to unfold the behavioral functions of this intriguing, yet complex, pathway. This review describes the current state of knowledge on the DDC with respect to its anatomy, connectivity, and functions in reward and aversion processes.

• Publication year

  2018

• Venue

  Behavioural Brain Research

• Publication date

  2018-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.bbr.2018.04.018PMID 29684476
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The roles of the orbitofrontal cortex via the habenula in non-reward and depression, and in the responses of serotonin and dopamine neurons.

  2017cited by this paper
• Learning shapes the aversion and reward responses of lateral habenula neurons

  2017cited by this paper
• Translating the Habenula-From Rodents to Humans.

  2017cited by this paper
• The role of the habenula in the transition from reward to misery in substance use and mood disorders.

  2017influential reference
• The habenula as a critical node in chronic stress‐related anxiety

  2017cited by this paper
• The habenula in psychiatric disorders: More than three decades of translational investigation

  2017influential reference
• Serotonin stimulates lateral habenula via activation of the post-synaptic serotonin 2/3 receptors and transient receptor potential channels.

  2016cited by this paper
• Habenula responses to potential and actual loss in major depression: preliminary evidence for lateralized dysfunction.

  2016cited by this paper
• Social conflict resolution regulated by two dorsal habenular subregions in zebrafish

  2016cited by this paper
• mGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output

  2016cited by this paper
• DREADDS: Use and application in behavioral neuroscience.

  2016cited by this paper
• Can the Lateral Habenula Crack the Serotonin Code?

  2016cited by this paper
• Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula

  2016cited by this paper
• Effect of electrolytic lesions of the dorsal diencephalic conduction system on the distribution of Fos-like immunoreactivity induced by rewarding electrical stimulation.

  2016cited by this paper
• Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Regulate Feeding and Reward

  2016cited by this paper
• Basal forebrain projections to the lateral habenula modulate aggression reward

  2016cited by this paper
• Serotonin modulates glutamatergic transmission to neurons in the lateral habenula

  2016cited by this paper
• Role of the dorsal diencephalic conduction system in the brain reward circuitry.

  2016cited by this paper
• Distribution of vesicular glutamate transporters in the human brain

  2015cited by this paper
• Efferent Pathways of the Mouse Lateral Habenula

  2015cited by this paper
• Habenula Lesions Reveal that Multiple Mechanisms Underlie Dopamine Prediction Errors.

  2015cited by this paper
• The Brain on Drugs: From Reward to Addiction.

  2015cited by this paper
• Increased Excitability of Lateral Habenula Neurons in Adolescent Rats following Cocaine Self-Administration

  2015cited by this paper
• Revisiting the Serotonin Hypothesis: Implications for Major Depressive Disorders

  2015cited by this paper
• Activation of serotonin(2C) receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat.

  2015cited by this paper
• The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion.

  2014cited by this paper
• 5HT(1B) receptor-mediated pre-synaptic depression of excitatory inputs to the rat lateral habenula.

  2014cited by this paper
• Reward processing by the lateral habenula in normal and depressive behaviors

  2014cited by this paper
• Expression of mu opioid receptor in dorsal diencephalic conduction system: new insights for the medial habenula.

  2014cited by this paper
• Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement

  2014cited by this paper
• Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat

  2014cited by this paper
• A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei.

  2014cited by this paper
• GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment

  2014cited by this paper
• The habenula encodes negative motivational value associated with primary punishment in humans

  2014cited by this paper
• Differential Expression and Function of Nicotinic Acetylcholine Receptors in Subdivisions of Medial Habenula

  2014cited by this paper
• A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward.

  2013cited by this paper
• The habenula governs the attribution of incentive salience to reward predictive cues

  2013cited by this paper
• The medial habenula as a regulator of anxiety in adult zebrafish

  2013cited by this paper
• Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior

  2013cited by this paper
• βCaMKII in Lateral Habenula Mediates Core Symptoms of Depression

  2013cited by this paper
• Patterns of mRNA and protein expression for 12 GABAA receptor subunits in the mouse brain

  2013cited by this paper
• Lateral habenula deep brain stimulation for personalized treatment of drug addiction

  2013cited by this paper
• Morphine dependence and withdrawal induced changes in cholinergic signaling.

  2013cited by this paper
• Dopamine D4 Receptor Excitation of Lateral Habenula Neurons via Multiple Cellular Mechanisms

  2013cited by this paper
• Neurodegeneration of lateral habenula efferent fibers after intermittent cocaine administration: implications for deep brain stimulation.

  2013cited by this paper
• Differential contribution of mesoaccumbens and mesohabenular dopamine to intracranial self-stimulation.

  2013influential reference
• Synaptic and cellular profile of neurons in the lateral habenula

  2013cited by this paper
• A new translational target for deep brain stimulation to treat depression

  2013cited by this paper
• Hyperactivation of the habenula as a link between depression and sleep disturbance

  2013cited by this paper
• Molecular characterization of the subnuclei in rat habenula

  2012cited by this paper
• Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin.

  2012cited by this paper
• Stimulation of Midbrain Dopaminergic Structures Modifies Firing Rates of Rat Lateral Habenula Neurons

  2012cited by this paper
• Differential projections from the lateral habenula to the rostromedial tegmental nucleus and ventral tegmental area in the rat

  2012cited by this paper
• α3β4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo.

  2012cited by this paper
• Mapping pain activation and connectivity of the human habenula.

  2012cited by this paper
• Input-specific control of reward and aversion in the ventral tegmental area

  2012cited by this paper
• Alpha 3 beta 4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo

  2012cited by this paper
• Unmasking the mysteries of the habenula in pain and analgesia.

  2012cited by this paper
• Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance

  2012cited by this paper
• Topography of descending projections from anterior insular and medial prefrontal regions to the lateral habenula of the epithalamus in the rat

  2012cited by this paper
• Lesions of the lateral habenula dissociate the reward-enhancing and locomotor-stimulant effects of amphetamine.

  2012cited by this paper
• Habenula Circuit Development: Past, Present, and Future

  2012cited by this paper
• Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration.

  2011cited by this paper
• Mesopontine rostromedial tegmental nucleus neurons projecting to the dorsal raphe and pedunculopontine tegmental nucleus: psychostimulant-elicited Fos expression and collateralization

  2011cited by this paper
• Optogenetic tools for analyzing the neural circuits of behavior.

  2011cited by this paper
• Morphological and electrophysiological characteristics of neurons within identified subnuclei of the lateral habenula in rat brain slices.

  2011cited by this paper
• Negative Reward Signals from the Lateral Habenula to Dopamine Neurons Are Mediated by Rostromedial Tegmental Nucleus in Primates

  2011influential reference
• Duration of Inhibition of Ventral Tegmental Area Dopamine Neurons Encodes a Level of Conditioned Fear

  2011cited by this paper
• Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression.

  2011cited by this paper
• Habenula "cholinergic" neurons co-release glutamate and acetylcholine and activate postsynaptic neurons via distinct transmission modes.

  2011cited by this paper
• Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression.

  2011influential reference
• Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior.

  2010cited by this paper
• Glutamatergic axons from the lateral habenula mainly terminate on GABAergic neurons of the ventral midbrain.

  2010cited by this paper
• Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient.

  2010cited by this paper
• Synaptic potentiation onto habenula neurons in learned helplessness model of depression

  2010cited by this paper
• Neurochemical phenotypes of the afferent and efferent projections of the mouse medial habenula.

  2009cited by this paper
• Dopaminergic activation excites rat lateral habenular neurons in vivo.

  2009cited by this paper
• Representation of negative motivational value in the primate lateral habenula

  2009influential reference
• The effects of tryptophan depletion on neural responses to emotional words in remitted depression.

  2009cited by this paper
• The mesopontine rostromedial tegmental nucleus: A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta

  2009cited by this paper
• Afferents to the GABAergic tail of the ventral tegmental area in the rat

  2009cited by this paper
• Rodent Habenulo–Interpeduncular Pathway Expresses a Large Variety of Uncommon nAChR Subtypes, But Only the α3β4* and α3β3β4* Subtypes Mediate Acetylcholine Release

  2009cited by this paper
• Lateral habenula projections to dopamine and GABA neurons in the rat ventral tegmental area

  2009cited by this paper
• The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain

  2008cited by this paper
• Electrolytic lesions of the habenula attenuate brain stimulation reward.

  2008cited by this paper
• The globus pallidus sends reward-related signals to the lateral habenula.

  2008cited by this paper
• Dopamine in drug abuse and addiction: results of imaging studies and treatment implications.

  2007cited by this paper
• 18‐MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens

  2007cited by this paper
• Dopaminergic projections from the VTA substantially contribute to the mesohabenular pathway in the rat.

  2007cited by this paper
• Lateral habenula as a source of negative reward signals in dopamine neurons

  2007influential reference
• Dual GABAergic synaptic response of fast excitation and slow inhibition in the medial habenula of rat epithalamus.

  2007cited by this paper
• Lateral Habenula Stimulation Inhibits Rat Midbrain Dopamine Neurons through a GABAA Receptor-Mediated Mechanism

  2007cited by this paper
• Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus

  2007cited by this paper
• Absence of GABA type A signaling in adult medial habenular neurons.

  2006cited by this paper
• Dendritic morphology, local circuitry, and intrinsic electrophysiology of neurons in the rat medial and lateral habenular nuclei of the epithalamus

  2005influential reference
• Schizophrenia in translation: the presence of absence: habenular regulation of dopamine neurons and the encoding of negative outcomes.

  2005cited by this paper
• OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR ECONOMIC SUBSTITUTABILITY OF ELECTRICAL BRAIN STIMULATION , FOOD , AND WATER

  2005cited by this paper
• Substance P afferents from the habenula innervate the dorsal raphe nucleus

  2004cited by this paper
• Ionic Mechanism of Long-Lasting Discharges of Action Potentials Triggered by Membrane Hyperpolarization in the Medial Lateral Habenula

  2004cited by this paper
• Dopamine in drug abuse and addiction: results from imaging studies and treatment implications

  2004cited by this paper

• Increased risk of suicide in substance use disorder: a neurobiological perspective

  2026cites this paper
• Effects of 3DVR-haptic simulation training on cognitive functions: a functional neuroimaging pilot study using swLORETA qEEG

  2026cites this paper
• The Clinical Impact of Habenular Dysfunction on Depression and Suicidality: A Literature Review and Discussion on the Implications for Psychiatric Practice

  2025cites this paper
• A Comprehensive Overview of Stress, Resilience, and Neuroplasticity Mechanisms

  2025cites this paper
• Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain

  2024cites this paper
• The putative role of the habenula in animal migration.

  2024cites this paper
• The Neuroanatomy of the Habenular Complex and Its Role in the Regulation of Affective Behaviors

  2024cites this paper
• Role of Neuroglia in the Habenular Connection Hub of the Dorsal Diencephalic Conduction System

  2023cites this paper
• Adhesion molecule Amigo2 is involved in the fasciculation process of the fasciculus retroflexus

  2022cites this paper
• Circuits Regulating Pleasure and Happiness - Focus on Potential Biomarkers for Circuitry including the Habenuloid Complex.

  2022cites this paper
• The Neuromeric/Prosomeric Model in Teleost Fish Neurobiology

  2022cites this paper
• Diversification of habenular organization and asymmetries in teleosts: Insights from the Atlantic salmon and European eel

  2022cites this paper
• Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra

  2021cites this paper
• Wnt1 Role in the Development of the Habenula and the Fasciculus Retroflexus

  2021cites this paper
• Adult Neurogenesis: A Story Ranging from Controversial New Neurogenic Areas and Human Adult Neurogenesis to Molecular Regulation

  2021cites this paper
• Trans-inhibition of axon terminals underlies competition in the habenulo-interpeduncular pathway.

  2021cites this paper
• Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons

  2021cites this paper
• The anterior and medial thalamic nuclei and the human limbic system: tracing the structural connectivity using diffusion-weighted imaging

  2020cites this paper
• Special issue to commemorate the intellectual contributions of Allan R. Wagner.

  2020cites this paper
• The human habenula is responsive to changes in luminance and circadian rhythm

  2019cites this paper
• Targeting the Recently Deorphanized Receptor GPR83 for the Treatment of Immunological, Neuroendocrine and Neuropsychiatric Disorders.

  2018cites this paper