Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain
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Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain. / Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H; Mikkelsen, Jens D.
In: Cerebral Cortex, Vol. 20, No. 9, 2010, p. 2092-102.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain
AU - Thomsen, Morten S
AU - Hay-Schmidt, Anders
AU - Hansen, Henrik H
AU - Mikkelsen, Jens D
PY - 2010
Y1 - 2010
N2 - alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions important for cognitive function. However, the neural substrates involved in these effects remain elusive. Here we identify cortically projecting cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain (BF) as important targets for alpha(7) nAChR activation, as measured by c-Fos immunoreactivity, a marker of neuronal activation. Selective depletion of these cholinergic neurons abolishes the SSR180711-induced activation of the mPFC but not the ACCshell, demonstrating their critical importance for alpha(7) nAChR-dependent activation of the mPFC. Contrarily, selective depletion of dopaminergic neurons in the ventral tegmental area abolishes the SSR180711-induced activation of the ACCshell but not the mPFC or HDB. These results demonstrate 2 distinct neural pathways activated by SSR180711. The BF and mPFC are important for attentional function and may subserve the procognitive effects of alpha(7) nAChR agonists, whereas activation of the ACCshell is implicated in the beneficial effect of antipsychotics on the positive symptoms of schizophrenia.
AB - alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions important for cognitive function. However, the neural substrates involved in these effects remain elusive. Here we identify cortically projecting cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain (BF) as important targets for alpha(7) nAChR activation, as measured by c-Fos immunoreactivity, a marker of neuronal activation. Selective depletion of these cholinergic neurons abolishes the SSR180711-induced activation of the mPFC but not the ACCshell, demonstrating their critical importance for alpha(7) nAChR-dependent activation of the mPFC. Contrarily, selective depletion of dopaminergic neurons in the ventral tegmental area abolishes the SSR180711-induced activation of the ACCshell but not the mPFC or HDB. These results demonstrate 2 distinct neural pathways activated by SSR180711. The BF and mPFC are important for attentional function and may subserve the procognitive effects of alpha(7) nAChR agonists, whereas activation of the ACCshell is implicated in the beneficial effect of antipsychotics on the positive symptoms of schizophrenia.
U2 - 10.1093/cercor/bhp283
DO - 10.1093/cercor/bhp283
M3 - Journal article
C2 - 20051354
VL - 20
SP - 2092
EP - 2102
JO - Cerebral Cortex
JF - Cerebral Cortex
SN - 1047-3211
IS - 9
ER -
ID: 21772439