Microarray analysis of transcripts with elevated expressions in the rat medial or lateral habenula suggest fast GABAergic excitation in the medial habenula and habenular involvement in the regulation of feeding and energy balance

Brain Struct Funct. 2016 Dec;221(9):4663-4689. doi: 10.1007/s00429-016-1195-z. Epub 2016 Feb 18.


In vertebrates the "anti-reward-system" mainly is represented by the habenula and its medial (MHb) and especially lateral (LHb) complexes. Considerable knowledge has accumulated concerning subnuclear structures and connectivities of MHb and LHb subnuclei. The present investigation aimed to obtain novel information, whether MHb or LHb or their subnuclei display field-characteristic gene products, which may shed light on biological functions of these areas. Unfortunately this was not the case. Microarray analysis of mRNAs in microdissected habenular and thalamic control areas yielded expression values of 17,745 RNAs representing protein-coding genes, to which annotated gene names could be assigned. High relative values of genes with known expression in MHb, LHb or thalamus in the corresponding areas indicated a high precision of the microdissection procedure. Note that the present report emphasizes differences between and not absolute expression values in the selected regions. The present investigation disclosed that the LHb genetically is much closer related to the thalamus as compared to the MHb. The results presented here focuse on gene transcripts related to major transmitter systems, catecholamines and neuropeptides. Quite surprisingly, our data indicate potentially inhibitory effects of acetylcholine and glutamate in the habenula. In addition, the absence of the K-Cl co-transporter 2 supports a largely excitatory role of GABAergic transmission especially in the MHb. Furthermore, several G-protein related receptors (Gpr83, Gpr139, Gpr149, Gpr151, Gpr158) and many neuropeptides related to feeding are differentially expressed in the habenular region, indicating that its involvement in the regulation of food consumption and energy expenditure may have been underestimated so far.

Keywords: KCC2; Lateral habenular complex (LHb); Medial habenular complex (MHb); Monaminergic systems; Neuropeptides; Non-reward system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Cannabinoids / metabolism
  • Dopamine / metabolism
  • Energy Metabolism*
  • Feeding Behavior*
  • Gene Expression Profiling
  • Gene Expression*
  • Glutamic Acid / metabolism
  • Habenula / cytology
  • Habenula / metabolism*
  • Habenula / physiology
  • Male
  • Neuropeptides / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Thalamus / metabolism
  • Tissue Array Analysis
  • gamma-Aminobutyric Acid / metabolism*


  • Cannabinoids
  • Neuropeptides
  • RNA, Messenger
  • Serotonin
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Acetylcholine
  • Dopamine