Elsevier

Life Sciences

Volume 102, Issue 1, 25 April 2014, Pages 49-54
Life Sciences

Influence of parafascicular thalamic input on neuronal activity within the nucleus accumbens is mediated by nitric oxide — An in vivo study

https://doi.org/10.1016/j.lfs.2014.02.029Get rights and content

Abstract

Aims

Thalamostriatal fibers are involved in cognitive tasks such as acquisition, learning, processing of sensory events, and behavioral flexibility and might play a role in Parkinson's disease. The aim of the present study was the in vivo electrochemical characterization of the projection from the lateral aspect of the parafascicular thalamus (Pfl) to the dorsolateral aspect of the nucleus accumbens (dNAc). Since nitric oxide (NO) plays a crucial role in striatal synaptic transmission, its implication in Pfl-evoked signaling within the dNAc was investigated.

Main methods

The Pfl was electrically stimulated utilizing paired pulses and extracellular potentials were recorded within the dNAc. Simultaneously, the dNAc was superfused using the push–pull superfusion technique for local application of compounds and for assessing the influence of NO on release of glutamate, aspartate and GABA.

Key findings

Stimulation of the Pfl evoked a negative-going component at 9–14 ms followed by a positive-going component at 39–48 ms. The early response was current-dependent and diminished by superfusion of the dNAc with tetrodotoxin, kynurenic acid or NG-nitro-l-arginine methyl ester (L-NAME), while 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PAPA/NO) increased this evoked potential. Transmitter release was inhibited by L-NAME and facilitated by PAPA/NO.

Significance

This study describes for the first time in vivo extracellular electrical responses of the dNAc on stimulation of the Pfl. Synaptic transmission within the dNAc on stimulation of the Pfl seems to be facilitated by NO.

Introduction

Thalamic projections to the striatum are involved in cognitive tasks such as acquisition, learning, processing of sensory events (Kato et al., 2011, Schulz et al., 2009), behavioral flexibility (Brown et al., 2010), and might play a role in Parkinson's disease (Galvan and Smith, 2011).

Nitric oxide (NO), a free radical, is known to interfere in synaptic transmission within striatal brain areas processing afferent signals which arise from different brain areas (Pierucci et al., 2011, West and Tseng, 2011).

The intralaminar thalamic nuclei, which are subdivided into a centromedian and parafascicular (Pf) part, are an essential source of thalamostriatal projections (Jones and Leavitt, 1974, Sadikot et al., 1992). In particular, fibers of the lateral aspect of the Pf (Pfl) innervate neostriatal brain areas such as the caudate putamen and the nucleus accumbens (Groenewegen and Berendse, 1994). Furthermore, the nucleus accumbens is innervated by cortical afferences (Brog et al., 1993). Both the corticostriatal and the thalamostriatal pathways have been suggested to utilize the excitatory amino acid glutamate as the neurotransmitter (Fonnum et al., 1981). Glutamate released from the thalamostriatal projections mainly operates through the N-methyl-d-aspartate (NMDA) type of ionotrophic glutamatergic receptors (MacDermott and Dale, 1987). Pf synapses also operate with postsynaptic NMDA receptors (Ellender et al., 2013). Activation of excitatory amino acid receptors promotes enzymatic synthesis of NO in postsynaptic structures (Garthwaite, 1991). Thus, parafascicular thalamic fibers might facilitate NO production by stimulation of striatal NMDA receptors.

In the present study we investigated the response of the dorsolateral aspect of the NAc (dNAc) to electrical stimulation of the Pfl. Furthermore, the possible role of NO in synaptic events within the dNAc was examined. For this purpose we used a push–pull superfusion device (Philippu, 1984) equipped with an extracellular electrode. Simultaneously, the dNAc release of glutamate, aspartate, and GABA was investigated under local application of compounds influencing NO synaptic level.

Section snippets

Animals

Protocols of experiments comply with the national guidelines for animal care and were approved by the Bundesministerium für Wissenschaft, Forschung und Kunst, Austria, Kommission für Tierversuchsangelegenheiten. The EU Directive 2010/63/EU for care and use of laboratory animals were followed. All procedures used were as humane as possible. Every effort was made to minimize the number of animals used and their suffering.

Animals were housed under constant temperature (23 ± 2 °C) and a 12 h light/dark

Results

Placements of the push–pull cannula with its recording electrode and of the stimulating electrode of all experiments are shown in Fig. 1. Cannulae were localized into the dNAc (Fig. 1a).

The Pfl paired pulse stimulation-evoked potentials in the dNAc usually consisted of a negative-going peak (first pulse response: N12, second pulse response: N′12) with a latency of 9 to 14 ms that was superimposed on a positive-going wave. In most of the experiments, N12 and N′12 were followed by a positive-going

Discussion

Thalamostriatal fibers are involved in cognitive tasks such as acquisition, learning, processing of sensory events (Kato et al., 2011, Schulz et al., 2009), behavioral flexibility (Brown et al., 2010), and might play a role in Parkinson's disease (Galvan and Smith, 2011).

In our study, stimulation by paired pulses of the PFl elicited characteristic extracellular potentials in the dNAc. The extracellular potentials consisted of one negative-going peak with a latency between 9 and 14 ms (N12,

Conclusions

In conclusion, we found in this study that the observed short-latency and short-lasting potentials evoked within the dNAc by stimulation of fibers arising from the Pfl are action potential- and glutamate-dependent and seem to be of polysynaptic origin. Furthermore NO plays a facilitatory role on synaptic transmission within the striatum via signals originating from the Pfl. Hence, NO might act as modulator in diseases affecting the thalamo-striatal pathways such as Parkinson's disease.

Conflict of interest

The authors declare that they have no conflict of interest

Acknowledgments

This work was supported by the “Fonds zur Förderung der Wissenschaftlichen Forschung”.

References (35)

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    Studies using the nNOS inhibitor NPA, revealed that both NO efflux and NADPH-d staining in the msNAc are robustly increased during intense, phasic activation of hippocampal inputs in a manner which is at least partially dependent on neuronal sources of NO. These studies are consistent with microdialysis studies showing that activation of the hippocampal fornix increases the release of GABA and NO via the activation of local interneurons in the NAc (Kraus and Prast, 2002). More recent studies by Prast and colleagues have showed that local field potentials evoked in the NAc during low frequency electrical stimulation of the parafascicular thalamus are attenuated by pretreatment with the non-selective NOS inhibitor l-NAME (Kraus et al., 2014), indicating that thalamic inputs may also drive NOS interneurons to synthesize and release NO in the msNAc. The activation of nNOS interneurons is most likely mediated via a direct effect of glutamatergic afferents as anatomical studies have shown that these neurons express NMDA receptor mRNA (Price et al., 1993) and protein (Gracy and Pickel, 1997).

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    Additionally, cortically evoked responses were depressed in nNOS KO mice as compared to wild-type controls (Padovan-Neto et al., 2015). Studies by Kraus et al. (2014) recently showed that local field potentials recorded in the NAc during low-frequency electrical stimulation of the parafascicular thalamus are attenuated by pretreatment with the nonselective NOS inhibitor l-NAME. In other pharmacological studies, systemic administration of the nNOS inhibitor 7-nitroindazole was found to strongly inhibit the spontaneous firing activity of striatal neurons isolated during low-frequency cortical stimulation (Ondracek et al., 2008).

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