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ENeuro Jul 2023The ventral pallidum (VP) is an integral locus in the reward circuitry and a major target of GABAergic innervation of both D1-medium spiny neurons (MSNs) and D2-MSNs...
The ventral pallidum (VP) is an integral locus in the reward circuitry and a major target of GABAergic innervation of both D1-medium spiny neurons (MSNs) and D2-MSNs from the nucleus accumbens. The VP contains populations of GABAergic [VPGABA, GAD2(+), or VGluT(-)] and glutamatergic [VPGlutamate, GAD2(-), or VGluT(+)] cells that facilitate positive reinforcement and behavioral avoidance, respectively. MSN efferents to the VP exert opponent control over behavioral reinforcement with activation of D1-MSN afferents promoting and D2-MSN afferents inhibiting reward seeking. How this afferent-specific and cell type-specific control of reward seeking is integrated remains largely unknown. In addition to GABA, D1-MSNs corelease substance P to stimulate neurokinin 1 receptors (NK1Rs) and D2-MSNs corelease enkephalin to activate μ-opioid receptors (MORs) and δ-opioid receptors. These neuropeptides act in the VP to alter appetitive behavior and reward seeking. Using a combination of optogenetics and patch-clamp electrophysiology in mice, we found that GAD2(-) cells receive weaker GABA input from D1-MSN, but GAD2(+) cells receive comparable GABAergic input from both afferent types. Pharmacological activation of MORs induced an equally strong presynaptic inhibition of GABA and glutamate transmission on both cell types. Interestingly, MOR activation hyperpolarized VPGABA but not VGluT(+). NK1R activation inhibited glutamatergic transmission only on VGluT(+) cells. Our results indicate that the afferent-specific release of GABA and neuropeptides from D1-MSNs and D2-MSNs can differentially influence VP neuronal subtypes.
Topics: Mice; Animals; Basal Forebrain; Neurons; Nucleus Accumbens; Neuropeptides; gamma-Aminobutyric Acid; Receptors, Opioid; Receptors, Dopamine D1; GABAergic Neurons
PubMed: 37414552
DOI: 10.1523/ENEURO.0404-22.2023 -
International Journal of Molecular... Mar 2024The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including locomotion, motivation,... (Review)
Review
The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including locomotion, motivation, cognition, reward, as well as maternal and reproductive behaviors. Dopamine is a neurotransmitter that binds to G-protein-coupled receptors. Dopamine also works together with other neurotransmitters and various neuropeptides to maintain the balance of synaptic functions. The dysfunction of the dopamine system leads to several conditions, including Parkinson's disease, Huntington's disease, major depression, schizophrenia, and drug addiction. The ventral tegmental area (VTA) has been identified as an important relay nucleus that modulates homeostatic plasticity in the midbrain dopamine system. Due to the complexity of synaptic transmissions and input-output connections in the VTA, the structure and function of this crucial brain region are still not fully understood. In this review article, we mainly focus on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, with the hope of obtaining new insight into the formation and function of this vital brain region.
Topics: Humans; Dopamine; Ventral Tegmental Area; Depressive Disorder, Major; Neuropeptides; Neurotransmitter Agents
PubMed: 38612683
DOI: 10.3390/ijms25073875 -
Annals of Surgery Aug 2023Report the 2-year outcomes of a multicenter randomized controlled trial comparing robotic versus laparoscopic intraperitoneal onlay mesh ventral hernia repair. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Report the 2-year outcomes of a multicenter randomized controlled trial comparing robotic versus laparoscopic intraperitoneal onlay mesh ventral hernia repair.
BACKGROUND
Ventral hernia repair is one of the most common operations performed by general surgeons. To our knowledge, no studies have been published to date comparing long-term outcomes of laparoscopic versus robotic ventral hernia repair.
METHODS
The trial was registered at clinicaltrials.gov (NCT03490266). Clinical outcomes included surgical site infection, surgical site occurrence, hernia occurrence, readmission, reoperation, and mortality.
RESULTS
A total of 175 consecutive patients were approached that were deemed eligible for elective minimally invasive ventral hernia repair. In all, 124 were randomized and 101 completed follow-up at 2 years. Two-year follow-up was completed in 54 patients (83%) in the robotic arm and 47 patients (80%) in the laparoscopic arm. No differences were seen in surgical site infection or surgical site occurrence. Hernia recurrence occurred in 2 patients (4%) receiving robotic repair versus in 6 patients (13%) receiving laparoscopic repair (relative risk: 0.3, 95% CI: 0.06-1.39; P =0.12). No patients (0%) required reoperation in the robotic arm whereas 5 patients (11%) underwent reoperation in the laparoscopic arm ( P =0.019, relative risk not calculatable due to null outcome).
CONCLUSIONS
Robotic ventral hernia repair demonstrated at least similar if not improved outcomes at 2 years compared with laparoscopy. There is potential benefit with robotic repair; however, additional multi-center trials and longer follow-up are needed to validate the hypothesis-generating findings of this study.
Topics: Humans; Robotic Surgical Procedures; Prospective Studies; Robotics; Laparoscopy; Hernia, Ventral; Herniorrhaphy; Surgical Wound Infection; Surgical Mesh
PubMed: 37203558
DOI: 10.1097/SLA.0000000000005903 -
IScience Sep 2023Patients with the sleep disorder narcolepsy suffer from excessive daytime sleepiness, disrupted nighttime sleep, and cataplexy-the abrupt loss of postural muscle tone...
Patients with the sleep disorder narcolepsy suffer from excessive daytime sleepiness, disrupted nighttime sleep, and cataplexy-the abrupt loss of postural muscle tone during wakefulness, often triggered by strong emotion. The dopamine (DA) system is implicated in both sleep-wake states and cataplexy, but little is known about the function of DA release in the striatum and sleep disorders. Recording DA release in the ventral striatum revealed orexin-independent changes across sleep-wake states as well as striking increases in DA release in the ventral, but not dorsal, striatum prior to cataplexy onset. Tonic low-frequency stimulation of ventral tegmental efferents in the ventral striatum suppressed both cataplexy and rapid eye movement (REM) sleep, while phasic high-frequency stimulation increased cataplexy propensity and decreased the latency to REM sleep. Together, our findings demonstrate a functional role of DA release in the striatum in regulating cataplexy and REM sleep.
PubMed: 37664637
DOI: 10.1016/j.isci.2023.107613 -
Scientific Reports Oct 2023Ménière's disease (MD) is associated with functional reorganization not only in the auditory or sensory cortex but also in other control and cognitive areas. In this...
Ménière's disease (MD) is associated with functional reorganization not only in the auditory or sensory cortex but also in other control and cognitive areas. In this study, we examined intranetwork and internetwork connectivity differences between 55 MD patients and 70 healthy controls (HC) in 9 well-defined resting-state networks. Functional connectivity degree was lower in MD compared to HC in 19 brain areas involved in the somatomotor, auditory, ventral attention, default mode, limbic, and deep gray matter networks. In addition, we observed lower intranetwork connectivity in the auditory, ventral attention, and limbic networks, as well as lower internetwork connectivity between the somatomotor and limbic networks, and between the auditory and somatomotor, deep gray matter, and ventral attention networks, and between the deep gray matter and default mode network. Furthermore, we identified 81 pairs of brain areas with significant differences in functional connectivity between MD patients and HC at the edge level. Notably, the left amygdala's functional connectivity degree was positively correlated with MD's disease stage, and the ventral attention network's intranetwork connectivity was positively correlated with the healthy side vestibular ratio. Our findings suggest that these functional network reorganization alterations may serve as potential biomarkers for predicting clinical progression, evaluating disease severity, and gaining a better understanding of MD's pathophysiology. Large-scale network studies using neuroimaging techniques can provide additional insights into the underlying mechanisms of MD.
Topics: Humans; Brain Mapping; Meniere Disease; Magnetic Resonance Imaging; Brain; Neuroimaging; Neural Pathways
PubMed: 37798378
DOI: 10.1038/s41598-023-44090-x -
Neuroscience Bulletin Feb 2024As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely...
As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats. Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions: the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli, whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties. Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors. Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats, whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain. These results provide direct evidence for the representations of nociceptive information in vCA1.
Topics: Rats; Animals; CA1 Region, Hippocampal; Hyperalgesia; Nociception; Neural Pathways; Hippocampus; Pyramidal Cells; Neuralgia
PubMed: 37440103
DOI: 10.1007/s12264-023-01086-x -
Cell Reports Nov 2023The insular cortex (IC) has been linked to the processing of interoceptive and exteroceptive signals associated with addictive behavior. However, whether the IC...
The insular cortex (IC) has been linked to the processing of interoceptive and exteroceptive signals associated with addictive behavior. However, whether the IC modulates the acquisition of drug-related affective states by direct top-down connectivity with ventral tegmental area (VTA) dopamine neurons is unknown. We found that photostimulation of VTA terminals of the anterior insular cortex (aIC) induces rewarding contextual memory, modulates VTA activity, and triggers dopamine release within the VTA. Employing neuronal recordings and neurochemical and transsynaptic tagging techniques, we disclose the functional top-down organization tagging the aIC pre-synaptic neuronal bodies and identifying VTA recipient neurons. Furthermore, systemic administration of amphetamine altered the VTA excitability of neurons modulated by the aIC projection, where photoactivation enhances, whereas photoinhibition impairs, a contextual rewarding behavior. Our study reveals a key circuit involved in developing and retaining drug reward-related contextual memory, providing insight into the neurobiological basis of addictive behavior and helping develop therapeutic addiction strategies.
Topics: Dopaminergic Neurons; Ventral Tegmental Area; Insular Cortex; Amphetamine; Reward
PubMed: 37924513
DOI: 10.1016/j.celrep.2023.113365 -
Neuron Jan 2024Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen...
Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.
Topics: Humans; Deep Brain Stimulation; Treatment Outcome; Obsessive-Compulsive Disorder; Ventral Striatum; Obsessive Behavior
PubMed: 37865084
DOI: 10.1016/j.neuron.2023.09.034 -
Journal of Craniovertebral Junction &... 2023Anterior craniocervical junction lesions have always been a challenge for neurosurgeons. Presenting with lower cranial nerve dysfunction and symptoms of brainstem...
CONTEXT
Anterior craniocervical junction lesions have always been a challenge for neurosurgeons. Presenting with lower cranial nerve dysfunction and symptoms of brainstem compression, decompression is often required. While posterior approaches offer indirect ventral brainstem decompression, direct decompression via odontoidectomy is necessary when they fail. The transoral and endoscopic endonasal approaches have been explored but come with their own limitations and risks. A novel retropharyngeal approach to the cervical spine has shown promising results with reduced complications.
AIMS
This study aims to explore the feasibility and potential advantages of the anterior retropharyngeal approach for accessing the odontoid process.
METHODS AND SURGICAL TECHNIQUE
To investigate the anatomical aspects of the anterior retropharyngeal approach, a paramedian skin incision was performed below the submandibular gland on two cadaveric specimens. The subcutaneous tissue followed by the platysma is dissected, and the superficial fascial layer is opened. The plane between the vascular sheath laterally and the pharyngeal structures medially is entered below the branching point of the facial vein and internal jugular vein. After reaching the prevertebral plane, further dissection cranially is done in a blunt fashion below the superior pharyngeal nerve and artery. Various anatomical aspects were highlighted during this approach.
RESULTS
The anterior, submandibular retropharyngeal approach to the cervical spine was performed successfully on two cadavers highlighting relevant anatomical structures, including the carotid artery and the glossopharyngeal, hypoglossal, and vagus nerves. This approach offered wide exposure, avoidance of oropharyngeal contamination, and potential benefit in repairing cerebrospinal fluid fistulas.
CONCLUSIONS
For accessing the craniocervical junction, the anterior retropharyngeal approach is a viable technique that offers many advantages. However, when employing this approach, surgeons must have adequate anatomical knowledge and technical proficiency to ensure better outcomes. Further studies are needed to enhance our anatomical variations understanding and reduce intraoperative risks.
PubMed: 38268697
DOI: 10.4103/jcvjs.jcvjs_112_23 -
Journal of Personalized Medicine Jan 2024Abdominal wall hernia repair, a common surgical procedure, includes various techniques to minimize postoperative complications and enhance outcomes. This review focuses... (Review)
Review
Abdominal wall hernia repair, a common surgical procedure, includes various techniques to minimize postoperative complications and enhance outcomes. This review focuses on the comparison between laparoscopic and robotic approaches in treating inguinal and ventral hernias, presenting the ongoing situation of this topic. A systematic search identified relevant studies comparing laparoscopic and robotic approaches for inguinal and ventral hernias. Randomized control trials, retrospective, and prospective studies published after 1 January 2000, were included. Search terms such as hernia, inguinal, ventral, laparoscopy, robotic, and surgery were used. A total of 23 articles were included for analysis. Results indicated similar short-term outcomes for robotic and laparoscopic techniques in inguinal hernia repair, with robotic groups experiencing less postoperative pain. However, longer operative times and higher costs were associated with robotic repair. Robotic ventral hernia repair demonstrated potential benefits, including shorter hospital stay, lower recurrence and lower reoperation rates. While robotic surgery offers advantages such as shorter hospital stays, faster recovery, and less postoperative pain, challenges including costs and training requirements need consideration. The choice between laparoscopic and robotic approaches for abdominal wall hernias should be tailored based on individual surgeon expertise and resource availability, emphasizing a balanced evaluation of benefits and challenges.
PubMed: 38248801
DOI: 10.3390/jpm14010100