Trans‐synaptic Modulation of Striatal ACh Release In Vivo by the Parafascicular Thalamic Nucleus

Abstract

Electrical stimulation of the parafascicular but not the ventrolateral or dorsomedial thalamic nucleus (ten 0.5 ms, 10 V pulses, 140 microA) of freely moving rats induced a frequency-dependent (2.5, 5, 10 and 20 Hz) increase in the extracellular acetylcholine (ACh) content of the dorsal striatum, assessed by trans-striatal microdialysis. The time-dependent effect of 10 Hz stimulation was studied. The peak increase, 39% above baseline, was attained during 4 min of stimulation. This was blocked by coperfusion with 5 microM tetrodotoxin, indicating that the release we measured represents a physiological process. The facilitatory effect of parafascicular nucleus stimulation does not appear to be associated with indirect action through the cerebral frontal cortex because 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 retroflexus in the facilitation of ACh release was also ruled out. The non-competitive NMDA-type receptor antagonist MK-801, applied by reversed dialysis (30 microM) or systemically injected (0.2 mg/kg), significantly reduced the basal ACh output and prevented the tetanus-evoked increase in ACh release. The results provide in vivo evidence that the activity of the cholinergic neurons in the dorsal striatum is trans-synaptically modulated by parafascicular nucleus excitatory afferents through activation of the NMDA subtype of glutamate receptors that is probably located in the striatum.

The thalamostriatal system in normal and diseased states

“…Using this preparation, the ratio of NMDA/non-NMDA glutamatergic receptors was found to be higher at thalamic than cortical synapses (Ding et al, 2008; Smeal et al, 2008), an observation that extends earlier neurochemical studies in adult rats (Baldi et al, 1995; Consolo et al, 1996a,b). This slice preparation has also lead to additional data suggesting that the thalamostriatal system gates corticostriatal signaling via activation of striatal cholinergic interneurons, and that this functional interaction might be altered in mouse model of dystonia (Ding et al, 2008; Sciamanna et al, 2012).…”

The Parafascicular Thalamic Nucleus Concomitantly Influences Behavioral Flexibility and Dorsomedial Striatal Acetylcholine Output in Rats

“…However, Bac-Mus infusions into several thalamic areas bordering the Pf did not impair reversal learning. Furthermore, stimulation of thalamic subregions and fiber tracts bordering the Pf do not affect striatal ACh output, in contrast to direct stimulation of the Pf (Baldi et al, 1995). Another possibility is that Pf inactivation altered striatal ACh output during reversal learning indirectly, by affecting activity in frontal cortex areas which project to the dorsomedial striatum.…”

Cholinergic interneurons in the dorsal and ventral striatum: anatomical and functional considerations in normal and diseased conditions

“…Prefrontal cortical inhibition and hippocampal activation induce N ‐methyl‐ d ‐aspartate (NMDA)–mediated release of acetylcholine in the accumbens, most likely through indirect routes that involve glutamatergic, GABAergic, and dopaminergic neurotransmitter systems . Other pharmacological studies suggested that thalamic inputs from Pf regulate ChIs activity predominantly through NMDA receptor activation, while the effects of cortical afferents are mainly mediated through AMPA receptor activation . Because of the limited information on the synaptic relationships between subtypes of glutamate receptors and their presynaptic afferent terminals from the cerebral cortex or thalamus, the underlying substrate for these specific glutamate receptor–mediated effects on ChIs is unknown.…”