ABSENCE OF CEREBELLAR LONG-TERM DEPRESSION IN MICE LACKING NEURONAL NITRIC-OXIDE SYNTHASE

Citation
V. Levram et al., ABSENCE OF CEREBELLAR LONG-TERM DEPRESSION IN MICE LACKING NEURONAL NITRIC-OXIDE SYNTHASE, Learning & memory, 4(1), 1997, pp. 169-177
Citations number
24
Categorie Soggetti
Psychology, Experimental",Neurosciences
Journal title
ISSN journal
10720502
Volume
4
Issue
1
Year of publication
1997
Pages
169 - 177
Database
ISI
SICI code
1072-0502(1997)4:1<169:AOCLDI>2.0.ZU;2-D
Abstract
Extensive pharmacological evidence suggests that nitric oxide (NO) is a crucial transmitter for cerebellar long-term depression (LTD), a lon g-lasting decrease in efficacy of the synapses from parallel fibers on to Purkinje neurons, triggered by coincident presynaptic activity and postsynaptic depolarization. We now show that LTD cannot be induced in Purkinje neurons under whole-cell patch clamp in cerebellar slices fr om young adult mice genetically lacking neuronal nitric oxide synthase (nNOS). This genetic evidence confirms the essentiality of NO and nNO S for LTD in young adult rodents, Surprisingly, LTD in cells from nNOS knockout mice cannot be rescued by photolytic uncaging of NO and cGMP inside Purkinje neurons, although such stimuli circumvent acute pharm acological inhibition of nNOS and soluble guanylate cyclase in normal rodents. Also slices from knockout mice show no deficit in cGMP elevat ion in response to exogenous NO. Therefore, prolonged absence of nNOS allows atrophy of the signaling pathway downstream of cGMP.