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.
"A new rat brain slice preparation that partly preserved thalamostriatal axons (Smeal et al., 2007) has enabled studies of the chemical and functional properties of thalamostriatal synapses and the potential relationships between thalamostriatal and corticostriatal systems in normal state (Ding et al., 2008; Smeal et al., 2008). 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). "
[Show abstract][Hide abstract] ABSTRACT: Because of our limited knowledge of the functional role of the thalamostriatal system, this massive network is often ignored in models of the pathophysiology of brain disorders of basal ganglia origin, such as Parkinson's disease (PD). However, over the past decade, significant advances have led to a deeper understanding of the anatomical, electrophysiological, behavioral and pathological aspects of the thalamostriatal system. The cloning of the vesicular glutamate transporters 1 and 2 (vGluT1 and vGluT2) has provided powerful tools to differentiate thalamostriatal from corticostriatal glutamatergic terminals, allowing us to carry out comparative studies of the synaptology and plasticity of these two systems in normal and pathological conditions. Findings from these studies have led to the recognition of two thalamostriatal systems, based on their differential origin from the caudal intralaminar nuclear group, the center median/parafascicular (CM/Pf) complex, or other thalamic nuclei. The recent use of optogenetic methods supports this model of the organization of the thalamostriatal systems, showing differences in functionality and glutamate receptor localization at thalamostriatal synapses from Pf and other thalamic nuclei. At the functional level, evidence largely gathered from thalamic recordings in awake monkeys strongly suggests that the thalamostriatal system from the CM/Pf is involved in regulating alertness and switching behaviors. Importantly, there is evidence that the caudal intralaminar nuclei and their axonal projections to the striatum partly degenerate in PD and that CM/Pf deep brain stimulation (DBS) may be therapeutically useful in several movement disorders.
Frontiers in Systems Neuroscience 01/2014; 8:5. DOI:10.3389/fnsys.2014.00005
"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. "
[Show abstract][Hide abstract] ABSTRACT: Recent evidence suggests that a circuit involving the centromedian-parafascicular (Pf) thalamus and basal ganglia is critical for a shift away from biased actions. In particular, excitatory input from the Pf onto striatal cholinergic neurons may facilitate behavioral flexibility. Accumulating evidence indicates that an endogenous increase in dorsomedial striatal acetylcholine (ACh) output enhances behavioral flexibility. The present experiments investigated whether the rat (Rattus norvegicus) Pf supports flexibility during reversal learning, in part, by modifying dorsomedial striatal ACh output. This was determined first by examining the effects of Pf inactivation, through infusion of the GABA agonists baclofen and muscimol, on place acquisition and reversal learning. Additional experiments examined Pf inactivation on dorsomedial striatal ACh output during reversal learning and a resting condition. Behavioral testing was performed in a cross-maze. In vivo microdialysis combined with HPLC/electrochemical detection was used to sample ACh from the dorsomedial striatum. Pf inactivation selectively impaired reversal learning in a dose-dependent manner. A subsequent study showed that an increase in dorsomedial striatal ACh efflux (∼30% above basal levels) during reversal learning was blocked by Pf inactivation, which concomitantly impaired reversal learning. In the resting condition, a dose of baclofen and muscimol that blocked a behaviorally induced increase in dorsomedial striatal ACh output did not reduce basal ACh efflux. Together, the present findings indicate that the Pf is an intralaminar thalamic nucleus critical for behavioral flexibility, in part, by directly affecting striatal ACh output under conditions that require a shift in choice patterns.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2010; 30(43):14390-8. DOI:10.1523/JNEUROSCI.2167-10.2010 · 6.34 Impact Factor
"Despite being responsive to the cortex, cholinergic interneurones are thought to receive relatively few cortical inputs (Scatton and Lehmann 1982) and the majority of excitatory inputs are thought to derive from the thalamus, particularly the parafascicular nucleus (Lapper and Bolam 1992). Afferents from the parafascicular nucleus enhance the release of striatal acetylcholine through NMDA receptor activation (Baldi et al. 1995) and stimulation of this area in vivo evokes EPSPs in cholinergic interneurones (Wilson et al. 1990). Some workers have suggested that the thalamus may be involved in controlling the irregular tonic firing pattern of the cholinergic interneurones since it exhibits a rhythmic tone that is associated with rhythmic firing in other areas of the forebrain (Von Krosigk et al. 1993). "
[Show abstract][Hide abstract] ABSTRACT: In the present study we have used single-cell RT-PCR in conjunction with electrophysiology to examine the expression and functional properties of metabotropic glutamate receptors (mGluRs) expressed within biochemically identified cholinergic interneurones in the rat striatum. Using single-cell RT-PCR, it was possible to demonstrate the presence of mGluR1, mGluR2, mGluR3, mGluR5 and mGluR7 mRNAs within single cholinergic interneurones. Bath application of the non-selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) or the group-I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) depolarized all cholinergic neurones tested by activation of an inward current at − 60 mV. The effects of DHPG were partially inhibited by the mGluR5 selective antagonist 6-methyl-2-(pherazo)-3-pyridinol and by the non-selective group-I antagonist α-methyl-4-carboxyphenylglycine but were not mimicked by the group-II and group-III selective mGluR agonists 2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) and l-2-amino-4-phosphonobutanoate (l-AP4), respectively. Intrastriatal stimulation evoked an excitatory postsynaptic current within cholinergic neurones that was reversibly inhibited by bath application of the group-II and group-III selective mGluR agonists DCG-IV and l-AP4, respectively, via presynaptic actions.
In summary, we have identified the mGluRs expressed by striatal cholinergic interneurones and demonstrated that their activation produces modulatory effects via both pre- and postsynaptic mechanisms.
Journal of Neurochemistry 05/2002; 81(1):142-9. DOI:10.1046/j.1471-4159.2002.00815.x · 4.28 Impact Factor
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