The Cerebral Cortex and Parafascicular Thalamic Nucleus Facilitate In vivo Acetylcholine Release in the Rat Striatum through Distinct Glutamate Receptor Subtypes

Abstract

Electrical stimulation (ten pulses of 0.5 ms, 10 V applied over 10 s at 10 Hz, 140 microA) delivered bilaterally to the prefrontal cortex or the parafascicular thalamic nucleus of freely moving rats facilitated acetylcholine release in dorsal striata, assessed by trans-striatal microdialysis. The facilitatory effects were blocked by coperfusion with 5 microM tetrodotoxin, suggesting that the release was of neuronal origin. The response of the striatal cholinergic neurons to prefrontal cortical stimulation was short-lived and required a longer period of stimulation (20 min) that the response to thalamic stimulation (4 min) to reach maximal effect. The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate glutamatergic receptor antagonist 6,7-dinitroquinoxaline-2,3-dione [DNQX; 12 nmol per side, intracerebroventricularly (i.c.v.)] and the AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX; 12 nmol per side, i.c.v. or 12.8 microM infused into the striatum), but not the NMDA-type receptor antagonist MK-801 (0.2 mg/kg, i.p.), abolished the facilitatory effect on striatal acetylcholine release evoked by stimulation of the prefrontal cortex. By contrast, DNQX or NBQX did not prevent the increase in striatal acetylcholine release evoked by parafascicular nucleus stimulation, but MK-801, in accordance with previous results, did so. MK-801 by itself lowered striatal acetylcholine output while DNQX and NBQX did not. The results provide in vivo evidence that the cerebral cortex facilitates cholinergic activity in the dorsal striatum apparently through the non-tonic activation of AMPA-type glutamatergic receptors while the parafascicular nucleus does this through tonic activation of NMDA receptors. Both glutamate receptor types are probably located in the striatum. The overall results suggest that the two pathways operate independently to regulate striatal cholinergic activity through distinct mechanisms.

The 5-HT6 Receptor Antagonist SB-271046 Selectively Enhances Excitatory Neurotransmission in the Rat Frontal Cortex and Hippocampus

“…Taken together, these data suggest that enhancement of glutamatergic function is not via a direct blockade of tonic serotonergic inhibition of glutamate neurons but is more likely to be an indirect action via the blockade of 5-HT 6 receptors on GABAergic interneurons either within, or on projection pathways to, the hippocampus and cortex. Whether the reported cholinergic effects ) are a consequence of this increase in glutamate or are an independent event (also mediated via GABA) cannot be determined from these experiments; however, interplay between the two systems has been demonstrated (Consolo et al 1996;Sanz et al 1997) and cannot be ruled out.…”

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

“…Finally, stimulation of medial PFC has diverse neurochemical effects, affecting several neurotransmitter systems besides 5-HT. Electrical stimulation of this area in rats enhances the levels of forebrain dopamine Fibiger 1993, 1995;Murase et al 1993) and acetylcholine (Taber and Fibiger 1994;Consolo et al 1996). It was also demonstrated that medial PFC stimulation activates noradrenergic neurons in the locus coeruleus (AstonJones et al 1991;Jodo et al 1998).…”

Cholinergic interneuron characteristics and nicotinic properties in the striatum

“…It is unlikely that the thalamic neurons are inhibitory in the usual sense, as the evidence currently available indicates that they are excitatory and employ glutamate as a transmitter (Wilson et al, 1983;Mouroux and Feger, 1993;Bevan et al, 1995). Direct stimulation of the thalamostriatal pathway also results in an increase of ACh release, which is sensitive to blockade by NMDA receptor antagonists (Consolo et al, 1996), suggesting a direct glutamatergic excitatory effect on cholinergic interneurons. Thus, thalamostriatal inputs onto the cholinergic neurons can exert significant excitatory control, but those afferents cannot completely explain the cholinergic firing pattern associated with the behavioral tasks.…”