INVESTIGADORES
SOIZA REILLY Mariano
congresos y reuniones científicas
Título:
Topographic analysis of ion channel mRNA distribution in mouse dorsal raphe nucleus using the Allen Brain Atlas
Autor/es:
SCOTT J. TEMPLIN; SUN JUNG BANG; MARIANO SOIZA REILLY; CHARLES B. BERDE; KATHRYN G. COMMONS
Lugar:
Washington
Reunión:
Congreso; 41st Society for Neuroscience Annual Meeting; 2011
Institución organizadora:
Society for Neuroscience
Resumen:
Neurons
in the dorsal raphe nucleus (DR) are the major source of serotonin
(5-hydroxytryptamine,
5-HT) in the forebrain. Altered 5-HT neurotransmission is implicated
in several neuropsychiatric disorders such as depression, anxiety, and
schizophrenia. Within the DR, 5-HT neurons have a characteristic
distribution primarily on the midline. In contrast,
non-5-HT neurons, particularly GABAergic neurons, tend to be located
lateral to the midline. 5-HT and non-5-HT neurons have also been
associated with different electrophysiological properties. To explore
the logical hypothesis that electrophysiological characteristics
of different groups of cells in the DR are driven by expression of
specialized ion channels we turned to the Allen Mouse Brain Atlas
(http://mouse.brain-map.org) a genome-wide database of high-throughput
in-situ hybridization data for 29,000 genes. We evaluated
the mRNA expression pattern of 142 voltage-gated and 72 ligand-gated
ion channels as listed by International Union of Basic and Clinical
Pharmacology (http://www.iuphar-db.org/). The expression pattern for
each of these genes was compared to that of tryptophan
hydroxylase 2 (TPH2), the rate-limiting enzyme for the synthesis of
5-HT. We screened for genes that had either enriched expression on the
midline, similar to a TPH2-pattern of expression, or appeared
selectively reduced along the midline, suggestive of
expression of non-5-HT cells. Genes that did not exhibit a pattern of
expression with respect to midline were eliminated. Less then 10% of the
screened genes showed patterned expression within the DR. These
included two voltage-gated sodium channels, SCN3b
and SCN1b; voltage-gated potassium channels KCNH8 (subfamily H) and
KCNK9 (M-channel); KCNJ6 (GIRK2); a voltage gated calcium channel,
CACNA1h (Cav3.2); KCNK9 (TASK-3); and a p/q type channel CACNA1A. Of
these, TASK-3 has previously been identified as enriched
in 5-HT neurons. Several GABA-A and glutamate (AMPA and kainate)
receptor subunits appeared enriched on the midline including GABRB1,
GABRG2, GABRG3, GRIA4, GRIK2 and GRIK5. A few receptor subunits had
reduced expression along the midline including GABRB2,
GABRA1 and GRIA3. Some of the identified genes had topographic
patterns of expression suggesting presence in selected subsets of
cells. Therefore, the Allen Brain Atlas may be used to uncover patterns
of DR ion channel distribution allowing for the identification
of novel pharmacologic targets to manipulate subgroups of DR neurons
and help define their roles in the pathophysiology of neuropsychiatric
disorders
