Two Distinct Neuronal Populations in the Rat Parafascicular Nucleus Oppositely Encode the Engagement in Stimulus-driven Reward-seeking.

BACKGROUND: The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years. METHODS: The parafascicular nucleus of the thalamus (Pf) has been implicated in the orientation of attention toward salient sensory stimuli. In a stimulus-driven reward-seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats. RESULTS: We observed a predominance of excitatory over inhibitory responses for all events in the task. Neurons responded more strongly to the stimulus compared to lever-pressing and reward collecting, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli between trials when animals were engaged in action and those when they were not. We distinguished two populations of neurons with opposite responses: MOTIV+ neurons responded more intensely to stimuli followed by a behavioral response than those that were not. Conversely, MOTIV- neurons responded more strongly when the animal did not respond to the stimulus. In addition, the latency of excitation of MOTIV- neurons was shorter than that of MOTIV+ neurons. CONCLUSION: Through this encoding, the Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level.

Dysconnectivity of the parafascicular nucleus in Parkinson's disease: A dynamic causal modeling analysis.

BACKGROUND: Recent animal model studies have suggested that the parafascicular nucleus has the potential to be an effective deep brain stimulation target for Parkinson's disease. However, our knowledge on the role of the parafascicular nucleus in Parkinson's disease patients remains limited. OBJECTIVE: We aimed to investigate the functional alterations of the parafascicular nucleus projections in Parkinson's disease patients. METHODS: We enrolled 72 Parkinson's disease patients and 60 healthy controls, then utilized resting-state functional MRI and spectral dynamic causal modeling to explore the effective connectivity of the bilateral parafascicular nucleus to the dorsal putamen, nucleus accumbens, and subthalamic nucleus. The associations between the effective connectivity of the parafascicular nucleus projections and clinical features were measured with Pearson partial correlations. RESULTS: Compared with controls, the effective connectivity from the parafascicular nucleus to dorsal putamen was significantly increased, while the connectivity to the nucleus accumbens and subthalamic nucleus was significantly reduced in Parkinson's disease patients. There was a significantly positive correlation between the connectivity of parafascicular nucleus-dorsal putamen projection and motor deficits. The connectivity from the parafascicular nucleus to the subthalamic nucleus was negatively correlated with motor deficits and apathy, while the connectivity from the parafascicular nucleus to the nucleus accumbens was negatively associated with depression. CONCLUSION: The present study demonstrates that the parafascicular nucleus-related projections are damaged and associated with clinical symptoms of Parkinson's disease. Our findings provide new insights into the impaired basal ganglia-thalamocortical circuits and give support for the parafascicular nucleus as a potential effective neuromodulating target of the disease.

Ten-m3 plays a role in the formation of thalamostriatal projections.

The importance of the thalamostriatal pathway for a myriad of brain functions is becoming increasingly apparent. Little is known about the formation of this pathway in mice. Further, while Ten-m3, a member of the Ten-m/teneurin/Odz family, is implicated in the proper wiring of mature thalamostriatal projections, its developmental time course is unknown. Here, we describe the normal development of thalamostriatal projections arising from the parafascicular nucleus (PFN) and show a role for Ten-m3 in its formation. Ten-m3 is expressed in both the PFN and the striatum by embryonic day 17 (E17). By postnatal day 3 (P3), it had a patchy appearance in the striatum, overlaid on a high dorsal-low ventral expression gradient in both structures. In wild-type mice, axons from the PFN begin to innervate the striatum by E17. By P3, terminals had ramified but were not confined to any striatal subregion. By P7, the axons had begun to avoid striosomes. The first indication of clustering of thalamic terminals within the striatal matrix was also seen at this time point. The compartmental targeting and clustering of PFN projections became more apparent by P10. Analysis of Ten-m3 knockout mice showed that while the early developmental progression of the thalamostriatal pathway is conserved, by P10 differences emerged, with a loss of topographic precision and the absence of terminal clustering. No evidence of the involvement of EphA7 downstream of Ten-m3 was found. Overall, our results suggest that Ten-m3 plays a role in the consolidation and refinement of thalamic axons to a specific subregion of the striatal matrix.

The role of the parafascicular thalamic nucleus in action initiation and steering.

The parafascicular (Pf) nucleus of the thalamus has been implicated in arousal and attention, but its contributions to behavior remain poorly characterized. Here, using in vivo and in vitro electrophysiology, optogenetics, and 3D motion capture, we studied the role of the Pf nucleus in behavior using a continuous reward-tracking task in freely moving mice. We found that many Pf neurons precisely represent vector components of velocity, with a strong preference for ipsiversive movements. Their activity usually leads velocity, suggesting that Pf output is critical for self-initiated orienting behavior. To test this hypothesis, we expressed excitatory or inhibitory opsins in VGlut2+ Pf neurons to manipulate neural activity bidirectionally. We found that selective optogenetic stimulation of these neurons consistently produced ipsiversive head turning, whereas inhibition stopped turning and produced downward movements. Taken together, our results suggest that the Pf nucleus can send continuous top-down commands that specify detailed action parameters (e.g., direction and speed of the head), thus providing guidance for orienting and steering during behavior.

Hyperkinetic Rat Model Induced by Optogenetic Parafascicular Nucleus Stimulation.

OBJECTIVE: The parafascicular nucleus (PF) plays important roles in controlling the basal ganglia. It is not well known whether the PF affects the development of abnormal involuntary movements (AIMs). This study was aimed to find a role of the PF in development of AIMs using optogenetic methods in an animal model. METHODS: Fourteen rats were underwent stereotactic operation, in which they were injected with an adeno-associated virus with channelrhodopsin (AAV2-hSyn-ChR2-mCherry) to the lateral one third of the PF. Behavior test was performed with and without optical stimulation 14 days after the injection of the virus. AIM of rat was examined using AIM score. After the behavior test, rat's brain was carefully extracted and the section was examined using a fluorescence microscope to confirm transfection of the PF. RESULTS: Of the 14 rats, seven rats displayed evident involuntary abnormal movements. AIM scores were increased significantly after the stimulation compared to those at baseline. In rats with AIMs, mCherry expression was prominent in the PF, while the rats without AIM lacked with the mCherry expression. CONCLUSION: AIMs could be reversibly induced by stimulating the PF through an optogenetic method.

Deep brain stimulation in the globus pallidus alleviates motor activity defects and abnormal electrical activities of the parafascicular nucleus in parkinsonian rats.

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD). The most common sites targeted for DBS in PD are the globus pallidus internal (GPi) and subthalamic nucleus (STN). However, STN-DBS and GPi-DBS have limited improvement in some symptoms and even aggravate disease symptoms. Therefore, discovering new targets is more helpful for treating refractory symptoms of PD. Therefore, our study selected a new brain region, the lateral globus pallidus (GP), as the target of DBS, and the study found that GP-DBS can improve motor symptoms. It has been reported that the thalamic parafascicular (PF) nucleus is strongly related to PD pathology. Moreover, the PF nucleus and GP have very close direct and indirect fiber connections. However, whether GP-DBS can change the activity of the PF remains unclear. Therefore, in this study, we monitored the activity changes in the PF nucleus in PD rats during a quiet awake state after GP-DBS. We found that GP-DBS could reverse the electrical activity of the PF nucleus in PD model rats, including the discharge pattern of the neurons and the local field potential (0.7-12 and 12-70 Hz). Based on the results mentioned above, PF activity in PD model rats could be changed by GP-DBS. Thus, the normalization of PF neuronal activity may be a potential mechanism for GP-DBS in the treatment of PD; these findings lay the foundation for PD treatment strategies.

Pathway-Specific Remodeling of Thalamostriatal Synapses in a Mouse Model of Parkinson's Disease.

BACKGROUND: The network pathophysiology underlying the motor symptoms of Parkinson's disease (PD) is poorly understood. In models of late-stage PD, there is significant cell-specific remodeling of corticostriatal, axospinous glutamatergic synapses on principal spiny projection neurons (SPNs). Neurons in the centrolateral nucleus (CLN) of the thalamus that relay cerebellar activity to the striatum also make axospinous synapses on SPNs, but the extent to which they are affected in PD has not been definitively characterized. OBJECTIVE: To fill this gap, transgenic mice in which CLN neurons express Cre recombinase were used in conjunction with optogenetic and circuit mapping approaches to determine changes in the CLN projection to SPNs in a unilateral 6-hydroxydopamine (6-OHDA) model of late-stage PD. METHODS: Adeno-associated virus vectors carrying Cre-dependent opsin expression constructs were stereotaxically injected into the CLN of Grp-KH288 mice in which CLN, but not parafascicular nucleus neurons, expressed Cre recombinase. The properties of this projection to identify direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) were then studied in ex vivo brain slices of the dorsolateral striatum from control and 6-OHDA lesioned mice using anatomic, optogenetic, and electrophysiological approaches. RESULTS: Optogenetically evoked excitatory synaptic currents in both iSPNs and dSPNs were reduced in lesioned mice; however, the reduction was significantly greater in dSPNs. In iSPNs, the reduction in evoked responses was attributable to synaptic pruning, because synaptic channelrhodopsin assisted circuit mapping (sCRACm) revealed fewer synapses per cell after lesioning. In contrast, sCRACm mapping of CLN inputs to dSPNs failed to detect any change in synapse abundance in lesioned mice. However, the ratio of currents through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors to those through N-methyl-D-aspartate receptors was significantly reduced in dSPNs. Moreover, the distribution of currents evoked by optical stimulation of individual synapses shifted toward smaller amplitudes by lesioning, suggesting that they had undergone long-term depression. CONCLUSIONS: Taken together, our results demonstrate that the CLN projection to the striatum undergoes a pathway-specific remodeling that could contribute to the circuit imbalance thought to drive the hypokinetic features of PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neural correlates of multidimensional motor outputs in an excitatory parafascicular-zona incerta circuit.

The parafascicular nucleus (Pf) in medial thalamus is interconnected with prefrontal cortex and basal ganglia. Though much research has determined its importance in cognitive regulation of behaviour, its projections to regions in subthalamus remain less known. Such connections include those to zona incerta (ZI), located immediately dorsal to subthalamic nuclei (STN) regulating motor output, and whose role in a motor context is only beginning to be investigated. We thus examined circuits from parafascicular (Pf) thalamus to ZI, and its activity during locomotion and spontaneous behaviours in mice. We found that a distinct group of CaMKIIα-positive excitatory parafascicular neurons, separated from VGLUT2-positive excitatory neurons, project widely into ZI, more than adjacent STN. Our results from fibre photometry and decoding with general linear model (GLM) indicate that PF-ZI pathways do not specifically correlate with amount of locomotion or movement velocity, but instead show more specified activity during relative directional changes of movements observed in turning, sniffing behaviours. These results hint at the PF-ZI pathway having a distinct role in directing action specificity and have implications for subcortical bases in dimensional control of behaviours.

Towards an expanded neuroscientific understanding of social play.

Play has been recognized as a complex and diverse set of behaviors that has been difficult to define. Play can range from rough and tumble play among rats to a human child playing a computer game. Play has been understood to exist in multiple forms such as social, object, and locomotor (Burghardt, 2005). In this article we review the literatures on the neural basis of social play, on heart rate variability, on behavioral switching and set-shifting, on prepulse inhibition of the acoustic startle reflex, and on learning at the level of the basal ganglia. Each of these neuronal pathways, aside from heart rate variability, is rooted in the parafascicular nucleus of the thalamus, an important neural substrate for social play. We argue that social play optimally balances a number of opposing neural pathways by engaging systems involved in safety versus danger (heart rate variability), automatized reactions versus learned reactions to new stimuli (behavioral switching and set-shifting), and gating relevant versus less relevant stimuli (prepulse inhibition of the acoustic startle reflex). The idea that play, in addition to its role in interpersonal adaptation to social life, may have a central role in optimizing flexibility and creativity in individual response to novelty has been explored by previous authors (Huizinga, 1955; Spinka et al., 2001; Pellegrini et al., 2007; Pellis and Pellis, 2017). In this paper we explore the possible underlying neural basis for this function of play, having to do with balancing various neural networks, and in doing so propose an expanded understanding of the nature and function of social play.

The zona incerta system: Involvement in attention and movement.

The zona incerta (ZI) is a large structure made of four neurochemically defined regions (at least, in rodents). It is globally involved in complex connections with telencephalic and brainstem centers. In this work, we focus on some of the anatomical links this structure develops with the cerebral cortex and the tectum. We also point to its integration within a larger basal ganglia network. The functions of this region are still mysterious, even if recent works suggest its participation in behavioral expression. Studies about the functional organization of the vibrissal system have provided the first integrated model, illustrating the ZI's role in sensory-motor programing. In addition, ZI connections with the superior colliculus and the cerebral cortex as well as recent behavioral studies point to this region playing a role in cognitive processes related to attention toward salient stimuli.

Edge-enhancing gradient echo with multi-image co-registration and averaging (EDGE-MICRA) for targeting thalamic centromedian and parafascicular nuclei.

BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus is an effective treatment for multiple neurological disorders. The centromedian and parafascicular nuclei are recently emerging targets for multiple conditions, such as epilepsy and Tourette syndrome; however, their limited visibility on conventional magnetic resonance imaging sequences has been a major obstacle. The goal of this study was to demonstrate the feasibility of a high-resolution and high-contrast targeting sequence for centromedian-parafascicular deep brain stimulation using a recently described magnetic resonance imaging sequence, three-dimensional edge-enhancing gradient echo. METHODS: The three-dimensional edge-enhancing gradient echo sequence was performed on a normal volunteer for a total of six acquisitions. Multi-image co-registration and averaging was performed by first co-registering each of the six scans and then averaging to produce an edge-enhancing gradient echo-multi-image co-registration and averaging scan. The averaging was also performed for two, three, four and five scans to assess the change in the signal-to-noise ratio and identify the ideal balance of image quality and scan time. RESULTS: The edge-enhancing gradient echo-multi-image co-registration and averaging scan allowed clear boundary delineation of the centromedian and parafascicular nuclei. The signal-to-noise ratio increased as a function of increasing scan number, but the added gain was small beyond four scans for the imaging parameters used in this study. CONCLUSIONS: The recently described three-dimensional edge-enhancing gradient echo sequence provides an easily implementable approach, using widely available magnetic resonance imaging technology without complex post-processing techniques, to delineate centromedian and parafascicular nuclei for deep brain stimulation targeting.

Analysis of morphological and neurochemical changes in subthalamic nucleus neurons in response to a unilateral 6-OHDA lesion of the substantia nigra in adult rats.

BACKGROUND: Subthalamic nucleus (STN) neurons undergo changes in their pattern of activity and morphology during the clinical course of Parkinson's disease (PD). Striatal dopamine depletion and hyperactivity of neurons in the parafascicular nucleus (Pf) of the intralaminar thalamus are predicted to contribute to the STN changes. OBJECTIVE: This study investigated possible morphological and neurochemical changes in STN neurons in a rat model of unilateral, nigral dopamine neuron loss, in relation to previously documented alterations in Pf neurons. METHODS: Male Sprague-Dawley rats received a unilateral injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNpc). Rats were randomly divided into two groups (6/group) for study at 1 and 5 months by post-treatment. The extent of SNpc dopamine neuron damage was assessed in an amphetamine-induced rotation test and postmortem assessment of tyrosine hydroxylase mRNA levels using in situ hybridization histochemistry. Neural cross-sectional measurements and assessment of vesicular glutamate transporter-2 (vGlut2) mRNA levels were performed to measure the impact on neurons in the STN. RESULTS: A unilateral SNpc dopaminergic neuron lesion significantly decreased the cross-sectional area of STN neurons ipsilateral to the lesion, at 1 month (P < 0.05) and 5 months (P < 0.01) post-lesion, while bilateral vGlut2 mRNA levels in STN neurons were unaltered. CONCLUSIONS: Decreased size of STN neurons in the presence of sustained vGlut2 mRNA levels following a unilateral SNpc 6-OHDA lesion, indicate altered STN physiology. This study presents further details of changes within the STN, coincident with observed alterations in Pf neurons and behaviour. DATA AVAILABILITY: The data associated with the findings of this study are available from the corresponding author upon request.

A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression.

While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABACeA) project to glutamatergic neurons in the parafascicular nucleus (GluPF). These GluPF neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing. Enhanced inhibition of the GABACeA→GluPF→S2 pathway is found in mice exhibiting CP symptoms. Reversing this pathway using chemogenetic or optogenetic approaches alleviates CP symptoms. Together, the current study demonstrates the putative importance of the GABACeA→GluPF→S2 pathway in controlling at least some aspects of CP.

Distinct Cortical-Thalamic-Striatal Circuits through the Parafascicular Nucleus.

The thalamic parafascicular nucleus (PF), an excitatory input to the basal ganglia, is targeted with deep-brain stimulation to alleviate a range of neuropsychiatric symptoms. Furthermore, PF lesions disrupt the execution of correct motor actions in uncertain environments. Nevertheless, the circuitry of the PF and its contribution to action selection are poorly understood. We find that, in mice, PF has the highest density of striatum-projecting neurons among all sub-cortical structures. This projection arises from transcriptionally and physiologically distinct classes of PF neurons that are also reciprocally connected with functionally distinct cortical regions, differentially innervate striatal neurons, and are not synaptically connected in PF. Thus, mouse PF contains heterogeneous neurons that are organized into parallel and independent associative, limbic, and somatosensory circuits. Furthermore, these subcircuits share motifs of cortical-PF-cortical and cortical-PF-striatum organization that allow each PF subregion, via its precise connectivity with cortex, to coordinate diverse inputs to striatum.

Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson's Disease Models.

The motor symptoms of Parkinson's disease (PD) are thought to stem from an imbalance in the activity of striatal direct- and indirect-pathway spiny projection neurons (SPNs). Disease-induced alterations in the activity of networks controlling SPNs could contribute to this imbalance. One of these networks is anchored by the parafascicular nucleus (PFn) of the thalamus. To determine the role of the PFn in striatal PD pathophysiology, optogenetic, chemogenetic, and electrophysiological tools were used in ex vivo slices from transgenic mice with region-specific Cre recombinase expression. These studies revealed that in parkinsonian mice, the functional connectivity of PFn neurons with indirect pathway SPNs (iSPNs) was selectively enhanced by cholinergic interneurons acting through presynaptic nicotinic acetylcholine receptors (nAChRs) on PFn terminals. Attenuating this network adaptation by chemogenetic or genetic strategies alleviated motor-learning deficits in parkinsonian mice, pointing to a potential new therapeutic strategy for PD patients.

The Critical Role of Intrinsic Membrane Oscillations.

Intrinsic, rhythmic subthreshold oscillations have been described in neurons of regions throughout the brain and have been found to influence the timing of action potentials induced by synaptic inputs. Some oscillations are sodium channel-dependent while others are calcium channel-dependent. These oscillations allow neurons to fire coherently at preferred frequencies and represent the main mechanism for maintaining high frequency network activity, especially in the cortex. Because cortical circuits are incapable of maintaining high frequency activity in the gamma range for prolonged periods, those processes dependent on continuous gamma band activity are subserved by subthreshold oscillations. As such, intrinsic oscillations, coupled with synaptic circuits, are essential to prolonged maintenance of such functions as sensory perception and "binding", problem solving, memory, waking, and rapid eye movement (REM) sleep.

Neuropsychological consequences of pallidal deep brain stimulation altering brain networks.

The purpose of this study was to evaluate postoperative changes in the neuropsychological function of cervical dystonia patients who had undergone deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and to investigate how DBS affects neuropsychological function by altering the neural networks of the brain. In 12 cervical dystonia patients, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to measure the preoperative and postoperative status of cervical dystonia, and the Seoul Neuropsychological Screening Battery was used to gather neuropsychological data. The data were analyzed using a Wilcoxon signed-rank test. The average improvement in the TWSTRS score at the time of the postoperative neuropsychological battery was 56.1 ±â€¯26.8%. In the neuropsychological battery, inhibitory control, as evaluated by the Stroop test, was significantly decreased after GPi DBS. The average pre-/postoperative Stroop test word and color reading correct response score were 107.9/99.2 (P = 0.043) and 85.3/75.8 (P = 0.032), respectively. The observed neuropsychological consequence of GPi DBS in this study, i.e., decreased inhibitory control, implies that electrical stimulation of the GPi may alter brain networks via the centromedian-parafascicular nuclear complex, suppressing the inhibitory control function of the prefrontal cortex.

The pedunculopontine and laterodorsal tegmental nuclei in the kainate model of epilepsy.

Prior studies showed that epilepsy can be associated with reorganization of the septohippocampal cholinergic fiber system. Using the kainate model of epilepsy, we wished to further examine the structural integrity of the mesopontine tegmental nuclei (pedunculopontine, PPN, and laterodorsal, LDT), which provide the cholinergic input to the thalamus. It was found that the total numbers of the PPN and LDT cells immunoreactive to the vesicular acetylcholine transporter did not differ between control and epileptic rats. However, the cholinergic cells had enlarged perikarya in epileptic rats. We further examined the effects of epilepsy on the distribution pattern of cholinergic fiber varicosities in the parafascicular nucleus, one of the principal thalamic targets of PPN projections. The density of cholinergic varicosities, represented by two distinct populations, was increased in epileptic rats. These data provide the first morphological evidence for structural alterations in mesopontine cholinergic neurons in experimental epilepsy. They suggest dysfunctional cholinergic transmission in the brainstem-thalamic pathway, which may partly account for various epilepsy-related neurological disturbances.

Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state: experience in 14 patients.

OBJECTIVE An effective treatment of patients in a minimally conscious state (MCS) or vegetative state (VS) caused by hypoxic encephalopathy or traumatic brain injury (TBI) is not yet available. Deep brain stimulation (DBS) of the thalamic reticular nuclei has been attempted as a therapeutic procedure mainly in patients with TBI. The purpose of this study was to investigate the therapeutic use of DBS for patients in VS or MCS. METHODS Fourteen of 49 patients in VS or MCS qualified for inclusion in this study and underwent DBS. Of these 14 patients, 4 were in MCS and 10 were in VS. The etiology of VS or MCS was TBI in 4 cases and hypoxic encephalopathy due to cardiac arrest in 10. The selection criteria for DBS, evaluating the status of the cerebral cortex and thalamocortical reticular formation, included: neurological evaluation, electrophysiological evaluation, and the results of positron emission tomography (PET) and MRI examinations. The target for DBS was the centromedian-parafascicular (CM-pf) complex. The duration of follow-up ranged from 38 to 60 months. RESULTS Two MCS patients regained consciousness and regained their ability to walk, speak fluently, and live independently. One MCS patient reached the level of consciousness, but was still in a wheelchair at the time the article was written. One VS patient (who had suffered a cerebral ischemic lesion) improved to the level of consciousness and currently responds to simple commands. Three VS patients died of respiratory infection, sepsis, or cerebrovascular insult (1 of each). The other 7 patients remained without substantial improvement of consciousness. CONCLUSIONS Spontaneous recovery from MCS/VS to the level of consciousness with no or minimal need for assistance in everyday life is very rare. Therefore, if a patient in VS or MCS fulfills the selection criteria (presence of somatosensory evoked potentials from upper extremities, motor and brainstem auditory evoked potentials, with cerebral glucose metabolism affected not more than the level of hypometabolism, which is judged using PET), DBS could be a treatment option.

Role of µ-opioid receptor in parafascicular nucleus of thalamus on morphine-induced antinociception in a rat model of acute trigeminal pain.

The parafascicular nucleus (PFN) of thalamus, as a supraspinal structure, has an important role in processing of nociceptive information. In addition, µ-opioid receptor contributes to supraspinal modulation of nociception. In the present study, the effects of microinjection of naloxone (a non-specific opioid-receptor antagonist) and naloxonazine (a specific µ-opioid receptor antagonist) were investigated on morphine-induced antinociception in a rat model of acute trigeminal pain. Right and left sides of PFN of thalamus were implanted with two guide cannulas. Acute trigeminal pain was induced by local corneal surface application of hypertonic saline and the number of eye wipes as a pain index was recorded for 30 sec. Microinjection of morphine at doses of 1, 2 and 4 µg per site significantly (p < 0.05) decreased the number of eye wipes. Alone microinjection of naloxone (4 µg per site) and naloxonazine (1 and 2 µg per site) significantly (p < 0.05) increased corneal pain severity. Prior microinjection of naloxone (2 and 4 µg per site) and naloxonazine (1 and 2 µg per site) significantly (p < 0.05) prevented the antinociceptive effect induced by morphine (4 µg per site). All the above-mentioned chemicals did not alter locomotor behavior in an open-field test. The results of the present study showed an antinociceptive effect of morphine at the PFN level of thalamus. Mu-opioid receptor of the PFN of thalamus may be involved in morphine-induced antinociception.