Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum.
To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone (Crh), the GABA transporter (Slc6a1), and prodynorphin (Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
Olsen
Christopher M
CM
Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Huang
Yong
Y
Goodwin
Shirlean
S
Ciobanu
Daniel C
DC
Lu
Lu
L
Sutter
Thomas R
TR
Winder
Danny G
DG
D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D016208:Databases, Factual; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018377:Neurotransmitter Agents / Q000235:genetics; D050479:Neurotransmitter Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D009714:Nucleus Accumbens / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D017981:Receptors, Neurotransmitter / Q000235:genetics; D012686:Septal Nuclei / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050479:Neurotransmitter Transport Proteins; D017981:Receptors, Neurotransmitter; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins