Neuroanatomical considerations for optimizing thalamic deep brain stimulation in Tourette syndrome.

OBJECTIVE: Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly used to treat severe Tourette syndrome, yielding promising outcomes. However, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. The authors aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses, including therapeutic and side effects. METHODS: The authors collected data from 8 patients with Tourette syndrome who were treated with DBS. The authors selected the active contact following threshold tests of acute side effects and gradually increased the stimulation intensity within the therapeutic window such that acute and chronic side effects could be avoided at each programming session. The patients were carefully interviewed, and stimulation-induced side effects were recorded. Clinical outcomes were evaluated using the Yale Global Tic Severity Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Hamilton Depression Rating Scale. The DBS lead location was evaluated in the normalized brain space by using a 3D atlas. The volume of tissue activated was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects. RESULTS: The mean follow-up period was 10.9 ± 3.9 months. All clinical scales showed significant improvement. Whereas the volume of tissue activated associated with therapeutic effects covers the centromedian and ventrolateral nuclei and showed an association with motor networks, those associated with paresthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed an association with limbic networks. CONCLUSIONS: This study addresses the importance of accurate implantation of DBS electrodes for obtaining standardized clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.

Minimally invasive trans-sulcal parafascicular surgical resection of cerebral tumors: translating anatomy to early clinical experience.

The minimally invasive port-based trans-sulcal parafascicular surgical corridor (TPSC) has incrementally evolved to provide a safe, feasible, and effective alternative to access subcortical and intraventricular pathologies. A detailed anatomical foundation is important in mitigating cortical and white matter tract injury with this corridor. Thus, the aims of this study are (1) to provide a detailed anatomical construct and overview of TPSCs and (2) to translate an anatomical framework to early clinical experience. Based on regional anatomical constraints, suitable parafascicular entry points were identified and described. Fiber tracts at both minimal and increased risks for each corridor were analyzed. TPSC-managed cases for metastatic or primary brain tumors were retrospectively reviewed. Adult patients 18 years or older with Karnofsky Performance Status (KPS) ≥ 70 were included. Subcortical brain metastases between 2 and 6 cm or primary brain tumors between 2 and 5 cm were included. Patient-specific corridors and trajectories were determined using MRI-tractography. Anatomy: The following TPSCs were described and translated to clinical practice: superior frontal, inferior frontal, inferior temporal, intraparietal, and postcentral sulci. Clinical: Eleven patients (5 males, 6 females) were included (mean age = 52 years). Seven tumors were metastatic, and 4 were primary. Gross total, near total, and subtotal resection was achieved in 7, 3, and 1 patient(s), respectively. Three patients developed intraoperative complications; all recovered from their intraoperative deficits and returned to baseline in 30 days. A detailed TPSC anatomical framework is critical in conducting safe and effective port-based surgical access. This review may represent one of the few early translational TPSC studies bridging anatomical data to clinical subcortical and intraventricular surgical practice.

The centromedian nucleus: Anatomy, physiology, and clinical implications.

Of all the truncothalamic nuclei, the centromedian-parafascicular nuclei complex (CM-Pf) is the largest and is considered the prototypic thalamic projection system. Located among the caudal intralaminar thalamic nuclei, the CM-Pf been described by Jones as "the forgotten components of the great loop of connections joining the cerebral cortex via the basal ganglia". The CM, located lateral relative to the Pf, is a major source of direct input to the striatum and also has connections to other, distinct region of the basal ganglia as well as the brainstem and cortex. Functionally, the CM participates in sensorimotor coordination, cognition (e.g. attention, arousal), and pain processing. The role of CM as 'gate control' function by propagating only salient stimuli during attention-demanding tasks has been proposed. Given its rich connectivity and diverse physiologic role, recent studies have explored the CM as potential target for neuromodulation therapy for Tourette syndrome, Parkinson's disease, generalized epilepsy, intractable neuropathic pain, and in restoring consciousness. This comprehensive review summarizes the structural and functional anatomy of the CM and its physiologic role with a focus on clinical implications.

The glycoprotein Ten-m3 mediates topography and patterning of thalamostriatal projections from the parafascicular nucleus in mice.

The striatum is the key input nucleus of the basal ganglia, and is implicated in motor control and learning. Despite the importance of striatal circuits, the mechanisms associated with their development are not well established. Previously, Ten-m3, a member of the Ten-m/teneurin/odz family of transmembrane glycoproteins, was found to be important in the mapping of binocular visual pathways. Here, we investigated a potential role for Ten-m3 in striatal circuit formation. In situ hybridisation revealed a patchy distribution of Ten-m3 mRNA expression superimposed on a high-dorsal to low-ventral gradient in a subregion of the striatal matrix. A survey of afferent/efferent structures associated with the matrix identified the parafascicular thalamic nucleus (PF) as a potential locus of action. Ten-m3 was also found to be expressed in a high-dorsal to low-ventral gradient in the PF, corresponding topographically to its expression in the striatum. Further, a subset of thalamic terminal clusters overlapped with Ten-m3-positive domains within the striatal matrix. Studies in wild-type (WT) and Ten-m3 knockout (KO) mice revealed no differences in overall striatal or PF structure. Thalamostriatal terminals in KOs, however, while still confined to the matrix subregion, lost their clustered appearance. Topography was also altered, with terminals from the lateral PF projecting ectopically to ventral and medial striatum, rather than remaining confined dorsolaterally as in WTs. Behaviorally, Ten-m3 KOs displayed delayed motor skill acquisition. This study demonstrates that Ten-m3 plays a key role in directing the formation of thalamostriatal circuitry, the first molecular candidate reported to regulate connectivity within this pathway.

Serotonergic fibers distribution in the midline and intralaminar thalamic nuclei in the rock cavy (Kerodon rupestris).

The thalamic midline/intralaminar complex is part of the higher-order thalamus, which receives little sensory input, and instead forms extensive cortico-thalamo-cortical pathways. The midline thalamic nuclei connect with the medial prefrontal cortex and the medial temporal lobe. On the other hand, the intralaminar nuclei connect with the fronto-parietal cortex. Taking into account this connectivity pattern, it is not surprising that the midline/intralaminar complex has been implicated in a broad variety of cognitive functions, including memory process, attention and orientation, and also reward-based behavior. Serotonin (5-HT) is a neurotransmitter that exerts different post-synaptic roles. Serotonergic neurons are almost entirely restricted to the raphe nuclei and the 5-HT fibers are distributed widely throughout the brain, including the midline/intralaminar complex. The present study comprises a detailed description of the morphologic features and semiquantitative analysis of 5-HT fibers distribution in the midline/intralaminar complex in the rock cavy, a typical rodent of the Northeast region of Brazil, which has been used by our group as an anatomical model to expand the comprehension about phylogeny on the nervous system. The 5-HT fibers in the midline/intralaminar nuclei of the rock cavy were classified into three distinct categories: (1) beaded fibers, which are relatively fine and endowed with large varicosities; (2) fine fibers, with thin axons and small varicosities uniformly distributed in whole axon; and (3) stem axons, showing thick non-varicose axons. Moreover, the density of 5-HT fibers is variable among the analyzed nuclei. On the basis of this diversity of the morphological fibers and the differential profile of optical density among the midline/intralaminar nuclei of the rock cavy, we conclude that the serotonergic system uses a diverse morphologic apparatus to exert a large functional repertory in the midline/intralaminar thalamic nuclei.

The neural connectivity of the intralaminar thalamic nuclei in the human brain: a diffusion tensor tractography study.

Research on the neural connectivity of the intralaminar thalamic nuclei (ILN) has been limited. Since the introduction of diffusion tensor imaging (DTI), many probabilistic DTI studies have reported on neural connectivity of neural structures in normal subjects. However, no study on the neural connectivity of the ILN has been reported so far. In this study, using probabilistic DTI, we investigated the neural connectivity of the ILN in normal subjects. A total of 40 healthy subjects were recruited for this study. A seed region of interest was placed on the ILN of the thalamus using the FMRIB Software Library. Connectivity was defined as the incidence of connection between the ILN and target brain areas. We found high connectivity between the ILN and arousal-related areas (prefrontal cortex 100%, reticular formation 100%, pedunculopontine nucleus 97.5%, basal forebrain 95%, and hypothalamus 92.5% at threshold 5), attention related area (prefrontal cortex 100% at threshold 5), and sensori-motor function related areas (primary motor cortex 100%, globus pallidus 100%, putamen 98.8%, premotor cortex 96.3%, primary somatosensory cortex 95.0%, caudate nucleus 92.5%, and posterior parietal cortex 90.0% at threshold 5). Findings of this study showed that ILN has high connectivity with brain areas related to arousal, attention, and sensorimotor function. This result indicates a close association of ILN with these functions in the human brain.

Projections of the central medial nucleus of the thalamus in the rat: node in cortical, striatal and limbic forebrain circuitry.

The central medial nucleus (CM) of thalamus is a prominent cell group of the rostral intralaminar complex of the thalamus. No previous report in the rat has comprehensively described the projections of CM. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we examined the efferent projections of CM, comparing projections from rostral (CMr) and caudal (CMc) regions of CM. We showed that the central medial nucleus distributes substantially to several cortical sites and to a limited number of subcortical structures. The primary CM targets were anterior and posterior regions of cortex, the claustrum, the caudate-putamen, the nucleus accumbens (ACC), the olfactory tubercle, and the amygdala. CMr and CMc distribute to several of the same structures but essentially to different parts of these structures. By comparison, CMr more strongly targets limbic structures, CMc more heavily sensorimotor structures. Main CMr projection sites were the medial agranular, anterior cingulate, prelimbic, dorsolateral orbital and dorsal agranular insular cortices, the dorsal striatum, the ACC, and the basolateral nucleus of the amygdala. Main CMc cortical projection sites were the ventrolateral, lateral and dorsolateral orbital cortices, dorsal, ventral and posterior agranular insular cortices, visceral cortex, primary somatosensory and motor cortices, and perirhinal cortex. Main CMc subcortical projection sites were the dorsal striatum and the lateral, central, anterior cortical, and basomedial nuclei of amygdala. The largely complementary output of CMr and CMc to diverse areas of cortex and to regions of the striatum and amygdala suggest a combined CM influence over a widespread area of the anterior cortex and throughout the dorsal and ventral striatum and the amygdala. CM projections to limbic and sensorimotor structures of the rostral forebrain suggest that CM may serve to integrate affective, cognitive and sensorimotor functions for goal-directed behavior.

Functional interaction between medial thalamus and rostral anterior cingulate cortex in the suppression of pain affect.

The medial thalamic parafascicular nucleus (PF) and the rostral anterior cingulate cortex (rACC) are implicated in the processing and suppression of the affective dimension of pain. The present study evaluated the functional interaction between PF and rACC in mediating the suppression of pain affect in rats following administration of morphine or carbachol (acetylcholine agonist) into PF. Vocalizations that occur following a brief noxious tailshock (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by injection of morphine or carbachol into PF. Vocalizations that occur during tailshock were suppressed to a lesser degree, whereas, spinal motor reflexes (tail flick and hindlimb movements) were only slightly suppressed by injection of carbachol into PF and unaffected by injection of morphine into PF. Blocking glutamate receptors in rACC (NMDA and non-NMDA) by injecting D-2-amino-5-phosphonovalerate (AP-5) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) produced dose-dependent antagonism of morphine-induced increases in vocalization thresholds. Carbachol-induced increases in vocalization thresholds were not affected by injection of either glutamate receptor antagonist into rACC. The results demonstrate that glutamate receptors in the rACC contribute to the suppression of pain affect produced by injection of morphine into PF, but not to the suppression of pain affect generated by intra-PF injection of carbachol.

[Posterior intralaminar nuclei of the thalamus and cognitive processes]. / Núcleos intralaminares posteriores del tálamo y procesos cognitivos.

INTRODUCTION: The parafascicular nucleus in rats and the centromedian parafascicular complex in primates and other mammals are the so-called posterior intralaminar nuclei (pIL) of the thalamus. Like the ascending reticular activating system and the basal ganglia-thalamocortical circuit, the pIL nuclei are part of the brain arousal systems. AIM: To describe and analyze different animal and human studies suggesting that the pIL could also be part of a neuro-physiological subcortical system related to cognitive processes as attention, learning and memory. DEVELOPMENT: Both parafascicular nucleus lesion studies in rats and neuropathological and neuroimaging reports in humans, indicate a relationship between the degeneration of pIL neurons and the cognitive deficits observed in learning and memory tasks in animals and also in several human neurological diseases and in consciousness disorders. CONCLUSIONS: Considering its neuroanatomical, neurophysiological and functional characteristics, the pIL can be considered excellent candidates for investigating cognitive processes in the field of psychobiology and clinical neurology.

Temporo-insular enhancement of EEG low and high frequencies in patients with chronic tinnitus. QEEG study of chronic tinnitus patients.

BACKGROUND: The physiopathological mechanism underlying the tinnitus phenomenon is still the subject of an ongoing debate. Since oscillatory EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions, this study investigates deviations from the norm of different resting EEG parameters in patients suffering from chronic tinnitus. RESULTS: Spectral parameters of resting EEG of male tinnitus patients (n = 8, mean age 54 years) were compared to those of age-matched healthy males (n = 15, mean age 58.8 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz. Using LORETA source analysis, the generators of delta, theta, alpha and beta power increases were localized dominantly to left auditory (Brodmann Areas (BA) 41,42, 22), temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas. CONCLUSIONS: Tinnitus patients show a deviation from the norm of different resting EEG parameters, characterized by an overproduction of resting state delta, theta and beta brain activities, providing further support for the microphysiological and magnetoencephalographic evidence pointing to a thalamocortical dysrhythmic process at the source of tinnitus. These results also provide further confirmation that reciprocal involvements of both auditory and associative/paralimbic areas are essential in the generation of tinnitus.

Delineation of the nucleus centre median by proton density weighted magnetic resonance imaging at 3 T.

OBJECTIVE: To demonstrate that proton density weighted magnetic resonance imaging (MRI) at 3 T accomplishes delineation of the centre median (CM) complex from surrounding thalamic tissue and may improve targeting accuracy in stereotactic neurosurgery. METHODS: Five healthy subjects (1 man, 4 women; age range 22-35 years) underwent high-resolution MRI at 3 T with different imaging parameters in order to optimize the direct visualization of the CM. RESULTS: In healthy subjects, the CM complex of the thalamus can be reliably contrasted on axially oriented slices by means of proton density weighted turbo-spin-echo MRI. An in-plane resolution of at least 0.6 x 0.6 mm2 is crucial at a slice thickness between 2 and 3 mm. Effective suppression of head motion is essential. CONCLUSION: MRI-based delineation of the CM could have therapeutic potential to facilitate target determination for neuromodulation in stereotactic neurosurgery.

Preliminary study in patients with obsessive-compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle.

OBJECTIVE: Deep brain stimulation has been used in the treatment of refractory obsessive-compulsive disorder (OCD). Our principal objective was to determine the safety and effectiveness of deep brain stimulation of the inferior thalamic peduncle in the treatment of refractory OCD. METHODS: An open protocol was performed from March 2003 to April 2007 in 5 patients with OCD refractory to conventional treatments. Bilateral stereotactic implantation of tetrapolar electrodes was aimed at the inferior thalamic peduncle and corroborated by electrophysiological responses and magnetic resonance imaging. All patients were off stimulation for 1 month after implantation. In the on-stimulation period, parameters were set at 5 V, 450 microseconds, 130 Hz in bipolar and continuous mode. Clinical changes were evaluated every 3 months for 12 months by means of the Yale-Brown Obsessive Compulsive Scale and the Global Assessment of Functioning scale. Statistical significance was assessed by the Friedman and Wilcoxon tests. RESULTS: The mean Yale-Brown Obsessive Compulsive Scale score decreased from 35 to 17.8 (P < 0.001), and the mean Global Assessment of Functioning scale score improved from 20% to 70% (P < 0.0001). The neuropsychological battery did not show significant changes, and there were no side effects related to electrical stimulation in the chronic period. CONCLUSION: We conclude that inferior thalamic peduncle stimulation is a safe procedure and may be an effective alternative in the treatment of those OCD cases refractory to conventional treatments.

Coherent gamma oscillations couple the amygdala and striatum during learning.

The basolateral amygdala (BLA) mediates the facilitating effects of emotions on memory. The BLA's enhancing influence extends to various types of memories, including striatal-dependent habit formation. To shed light on the underlying mechanisms, we carried out unit and local field potential (LFP) recordings in BLA, striatum, auditory cortex and intralaminar thalamus in cats trained on a stimulus-response task in which the presentation of one of two tones predicted reward delivery. The coherence of BLA, but not of cortical or thalamic, LFPs was highest with striatal gamma activity, and intra-BLA muscimol infusions selectively reduced striatal gamma power. Moreover, coupling of BLA-striatal unit activity increased when LFP gamma power was augmented. Early in training, the rewarded and unrewarded tones elicited a modest increase in coherent BLA-striatal gamma. As learning progressed, this gamma coupling selectively increased in relation to the rewarded tone. Thus, coherent gamma oscillations coordinate amygdalostriatal interactions during learning and might facilitate synaptic plasticity.

The primate centromedian-parafascicular complex: anatomical organization with a note on neuromodulation.

In addition to the cerebral cortex, the striatum receives excitatory input from the thalamus. The centromedian (centre median, CM) and parafascicular (Pf) nuclei are an important source of thalamostriatal projections. Anterograde tract-tracing indicates the CM-Pf complex provides dense afferents to the matrix compartment of the striatum. Whereas CM projects to the entire sensorimotor territory of the striatum, the Pf provides complementary input to the entire associative sector. The Pf also provides lighter input to the nucleus accumbens. Both CM and Pf provide light to moderately dense inputs to other components of the basal ganglia in a largely complementary manner, covering motor or associative-limbic territories of the subthalamic nucleus, globus pallidus and ventral midbrain. In turn, the CM and Pf receive mainly segregated input from parallel motor and associative-limbic circuits of the basal ganglia. The CM and Pf may therefore be considered important participants in parallel processing of motor and associative-limbic information in the basal ganglia. Connections of the CM and Pf with other thalamic nuclei suggest they also participate in integrative functions within the thalamus. In addition, inputs from the brainstem reticular core, reciprocal connections with the cerebral cortex and reticular thalamic nucleus suggest a role in state-dependant information processing. Consideration of the differential connections of the CM and Pf, and better understanding of their role in pathophysiology, may eventually lead to development of an important new target for relief of a variety of neurological and psychiatric disorders.

Roles of the thalamic CM-PF complex-Basal ganglia circuit in externally driven rebias of action.

The centromedian (CM)-parafascicular (PF) nuclear complex in the primate thalamus has reciprocal and specific connections with the basal ganglia. It has been argued that the thalamic CM-PF complex has a role in pain processing and attention. However, the functional relationship of this complex with the basal ganglia, which is considered to have a role in goal-directed movement, has not been well characterized. Here we present a hypothetical view that the thalamic CM-PF complex-basal ganglia circuit plays complementary roles in response bias. The basal ganglia are involved in creating 'reward-based pre-action bias', which facilitates the selection and execution of an action associated with a higher value. In contrast, when an action with a lower value is unexpectedly requested, the CM-PF induces an 'externally driven rebiasing' process in the striatum that aborts the pre-action bias and assists selecting and executing actions appropriate for unexpected situations. This model provides a framework for how the thalamic CM-PF complex and the basal ganglia function together in general for unexpected situations.

GABAergic and non-GABAergic thalamic, hypothalamic and basal forebrain projections to the ventral oral pontine reticular nucleus: their implication in REM sleep modulation.

The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. Some of these connections utilize the inhibitory neurotransmitter GABA. The aim of the present work is to map the local origin of the basal forebrain and diencephalon projections to the vRPO whether GABAergic or non-GABAergic. A double-labelling technique combining vRPO injections of the neuronal tracer, cholera-toxin (CTB), with GAD-immunohistochemistry, was used for this purpose in adult cats. All of the numerous CTB-positive neurons in the reticular thalamic and dorsocaudal hypothalamic nuclei were double-labelled (CTB/GAD-positive) neurons. Approximately 15%, 14% and 16% of the CTB-positive neurons in the zona incerta and the dorsal and lateral hypothalamic areas are, respectively, CTB/GAD-positive neurons. However, only some double-labelled neurons were found in other hypothalamic nuclei with abundant CTB-positive neurons, such as the paraventricular nucleus, perifornical area and H1 Forel field. In addition, CTB-positive neurons were abundant in the central amygdaline nucleus, terminal stria bed nuclei, median preoptic nucleus, medial and lateral preoptic areas, dorsomedial and ventromedial hypothalamic nuclei, posterior hypothalamic area and periventricular thalamic nucleus. The GABAergic and non-GABAergic connections described here may be the morphological pillar through which these prosencephalic structures modulate, either by inhibiting or by exciting, the vRPO REM-sleep inducing neurons during the different sleep-wakefulness cycle states.

Striatal projections of the vagal-responsive region of the thalamic parafascicular nucleus in macaque monkeys.

We recently reported that the thalamic parafascicular nucleus (Pf) in monkeys is strongly activated by vagus nerve afferents. The main forebrain target of Pf is the striatum, but the specific striatal regions receiving visceral input via this pathway are unknown. We examined the projections of this region by injecting anterograde tracers into the vagus evoked potential (VEP) focus in Pf of macaque monkeys. The VEP was strongest lateral and anterior to the habenulointerpeduncular tract, but it was distributed across the entire horizontal extent of the ventral half of Pf. All injections produced labeled terminals in the caudate (Cd), especially the Cd tail and the adjacent ventral posterior Pu. Terminations occurred throughout the Cd head and body but spared the most anterior and dorsolateral parts. Injections in more anterior and lateral portions of Pf produced progressively more terminations in Pu, mainly in the precommissural region and the medial aspect of posterior Pu. Dual injections of different tracers revealed overlapping projections with interdigitated strands of striatal terminations from separate regions of Pf as well as the posteromedial to anterolateral topographic gradient of increasing Pf projections to Pu. An injection in the most anteromedial portion of Pf produced strong labeling in the ventral striatum. Thus, Pf transmits viscerosensory information to the "associative" and "limbic" territories of the striatum. These findings suggest the broad involvement of homeostatic afferent activity in striatal function and perhaps a role for the striatum in autonomic function.

Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus.

Vesicular glutamate transporters (VGLUTs) are responsible for glutamate trafficking and for the subsequent regulated release of this excitatory neurotransmitter at the synapse. Three isoforms of the VGLUT have been identified, now known as VGLUT1, VGLUT2, and VGLUT3. Both VGLUT1 and VGLUT2 have been considered definitive markers of glutamatergic neurons, whereas VGLUT3 is expressed in nonglutamatergic neurons such as cholinergic striatal interneurons. It is widely believed that VGLUT1 and VGLUT2 are expressed in a complementary manner at the cortical and thalamic levels, suggesting that these glutamatergic neurons fulfill different physiological functions. In the present work, we analyzed the pattern of VGLUT1 and VGLUT2 mRNA expression at the thalamic level by using single and dual in situ hybridization. In accordance with current beliefs, we found significant expression of VGLUT2 mRNA in all the thalamic nuclei, while moderate expression of VGLUT1 mRNA was consistently found in both the principal relay and the association thalamic nuclei. Interestingly, individual neurons within these nuclei coexpressed both VGLUT1 and VGLUT2 mRNAs, suggesting that these individual thalamic neurons may have different ways of trafficking glutamate. These results call for a reappraisal of the previously held concept regarding the mutually exclusive distribution of VGLUT transporters in the central nervous system.

Connections of the zona incerta to the reticular nucleus of the thalamus in the rat.

This study demonstrated that there is a pathway from the zona incerta to the thalamic reticular nucleus. Injections of horseradish peroxidase or Fluorogold were made, using stereotaxic coordinates, into the rostral, intermediate or caudal regions of the thalamic reticular nucleus of adult Sprague-Dawley rats. The results show that the different regions of the thalamic reticular nucleus have distinct patterns of connections with the sectors of the zona incerta. In terms of the relative strength of the connections, injections made into the rostral regions of the thalamic reticular nucleus showed the highest number of labelled cells within the rostral and ventral sectors of the zona incerta; injections made into the intermediate regions of the thalamic reticular nucleus showed labelled cells in the dorsal and ventral sectors; while injections to the caudal regions of the thalamic reticular nucleus showed only a few labelled cells in the caudal sector of the zona incerta. Previous studies have shown that the zona incerta projects to the higher order thalamic nuclei but not first order thalamic nuclei. The labelling observed in the present study may represent collaterals of zona incerta to higher order thalamic nuclei projections.