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
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.