TRANSSYNAPTIC MODULATION OF STRIATAL ACH RELEASE IN-VIVO BY THE PARAFASCICULAR THALAMIC NUCLEUS

Electrical stimulation of the parafascicular but not the ventrolateral or dorsomedial thalamic nucleus (ten 0.5 ms, 10 V pulses, 140 mu A) o f freely moving rats induced a frequency-dependent (2.5, 5, 10 and 20 Hz) increase in the extracellular acetylcholine (ACh) content of the d orsal striatum, assessed by trans-striatal microdialysis. The time-dep endent effect of 10 Hz stimulation was studied. The peak increase, 39% above baseline, was attained during 4 min of stimulation. This was bl ocked by coperfusion with 5 mu M tetrodotoxin, indicating that the rel ease we measured represents a physiological process. The facilitatory effect of parafascicular nucleus stimulation does not appear to be ass ociated with indirect action through the cerebral frontal cortex becau se acute lesion of the excitatory corticostriatal afferents, which by itself reduced basal ACh release by 40%, did not modify the effect of 10 Hz stimulation. The possible involvement of the fasciculus retrofle xus in the facilitation of ACh release was also ruled out. The non-com petitive NMDA-type receptor antagonist MK-801, applied by reversed dia lysis (30 mu M) or systemically injected (0.2 mg/kg), significantly re duced the basal ACh output and prevented the tetanus-evoked increase i n ACh release. The results provide in vivo evidence that the activity of the cholinergic neurons in the dorsal striatum is trans-synapticall y modulated by parafascicular nucleus excitatory afferents through act ivation of the NMDA subtype of glutamate receptors that is probably lo cated in the striatum.