Long-range GABAergic projections from the nucleus of the solitary tract

The nucleus of the solitary tract (NTS) plays a crucial role in integrating peripheral information regarding visceral functions. Glutamate decarboxylase 2 (GAD2) inhibitory neurons are abundant in the NTS, and are known to form local and short-range projections within the NTS and nearby hindbrain areas. Here we performed whole-brain mapping of outputs from GAD2 neurons in the NTS using cell-type specific viral labeling together with ultrahigh-speed 3D imaging at 1-μm resolution. In addition to well-known targets of NTS GAD2 neurons including the principle sensory nucleus of the trigeminal (PSV), spinal nucleus of the trigeminal (SPV), and other short-range targets within the hindbrain, the high sensitivity of our system helps reveal previously unknown long-range projections that target forebrain regions, including the bed nuclei of the stria terminalis (BST) involved in stress and fear responses, and the paraventricular hypothalamic nucleus (PVH) involved in energy balance and stress-related neuroendocrine responses. The long-range projections were further verified by retrograde labeling of NTS GAD2 neurons with cholera toxin B (CTB) injections in the BST and PVH, and by Cre-dependent retrograde tracing with rAAV2-retro injections in the two regions of GAD2-Cre mice. Finally, we performed complete morphological reconstruction of several sparsely labeled neurons projecting to the forebrain and midbrain. These results provide new insights about how NTS might participate in physiological and emotional modulation.

Focused Ultrasound Thalamotomy Sensory Side Effects Follow the Thalamic Structural Homonculus

Introduction:Focused ultrasound thalamotomy is an effective treatment for tremor, however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects as well as their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML).Methods:Sensory adverse effects were categorized into four groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemi-body/limb paresthesia, and dysgeusia. Then, areas of significant risk (ASR) for each category were defined using voxel-wise mass univariate analysis and overlaid on corresponding odds ratio maps. The ASR area associated with the maximum risk was used as a region-of-interest in a normative functional connectome to determine side-effect specific functional connectivity. Finally, each ASR was overlaid on the medial lemniscus derived from normative template.Results:Of 103 patients, 17 developed sensory side effects after thalamotomy persisting 3 months after the procedures. Lesions producing sensory side effects extended posteriorly into the principle sensory nucleus of the thalamus or below the thalamus in the ML. The topography of sensory adverse effects followed the know somatotopy of the ML and the sensory nucleus. Functional connectivity patterns between each sensory-specific thalamic seed and the primary somatosensory areas supported the role of the middle insula in processing of gustatory information and in multisensory integration.Discussion:Distinct regions in the sensory thalamus and its afferent connections rise to specific sensory disturbances. These findings demonstrate the relationship between the sensory thalamus, ML, and bilateral sensory cortical areas.

P.118 Trigemino-cardiac reflex: a case report of intra-operative asystole in response to manipulation of the temporalis muscle

Background: The trigemino-cardiac reflex (TCR) is a sudden onset of bradycardia, hypotension, apnea or gastric hypermotility during stimulation of the trigeminal nerve. Methods: We conducted a MEDLINE search for surgical cases of TCR and herein describe a case seen recently at our institution. Results: A 60 year-old female underwent a left orbitozygomatic craniotomy for resection of a skull-base tumor. Pre-operative anesthesia evaluation was unremarkable and negative for a history of cardiovascular disease. Intra-operatively, retraction with moderate force of the temporalis muscle consistently produced asystole. Cessation of retraction resulted in immediate return of sinus rhythm. Otherwise, intra-operative heart rate was 60-90 BPM. Post-operatively, vital signs and clinical course were unremarkable. The patient experienced a similar phenomenon during an operation 6 years earlier, when manipulation of tumor near cranial nerves IX/X resulted in bradycardia. TCR is the result of a polysynaptic brainstem network involving the afferent trigeminal sensory nucleus, the reticular formation, and the efferent vagal motor nucleus. Conclusions: This is a case of exaggerated vagal response following manipulation of the temporalis muscle. Our report emphasizes the importance for neurosurgeons and anesthesiologists alike to be wary of TCR in order to avoid deleterious consequences when operating on structures associated with the trigeminal nerve.

Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal)

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms.