Alternate levels versus all levels mini-plate fixation in C3-6 cervical laminoplasty: a retrospective comparative study.

OBJECTIVE: The purpose of this study is to compare radiological and clinical outcomes between alternate levels (C4 and C6) and all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. METHODS: Ninety-six patients who underwent C3-6 unilateral open-door laminoplasty with alternate levels mini-plate fixation (54 patients in group A) or all levels mini-plate fixation (42 patients in group B) between September 2014 and September 2019 were reviewed in this study. Radiologic and clinical outcomes were assessed. Clinical results included Visual Analogue Scale (VAS) of axial neck pain and Japanese Orthopedic Association (JOA) score. Radiographic results included cervical range of motion (ROM), cervical curvature index (CCI), and the spinal canal expansive parameters including open angle, anteroposterior diameter (APD), and Pavlov`s ratio. RESULTS: There was no significant difference in VAS, JOA score, ROM, and CCI between two groups. There was no significant difference in canal expansion postoperatively between two groups. However, open angle, APD, and Pavlov`s ratio in group A decreased significantly during the follow-up. In group B, APD, Pavlov`s ratio, and open angle were maintained until the final follow-up. There was no hardware failure or lamina reclosure occurred in both groups during the follow-up. The mean cost of group B was higher than that of group A. CONCLUSIONS: Despite the differences in the maintenance of canal expansion, alternate levels mini-plate fixation can achieve similar clinical outcomes as all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. As evidenced in this study, we believe C3-6 laminoplasty with alternate levels (C4 and C6) mini-plate fixation is an economical, effective, and safe treatment method.

Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats.

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents. In vivo electrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.

Suppression of ventral hippocampal CA1 pyramidal neuronal activities enhances water intake.

Thirst is an important interoceptive response and drives water consumption. The hippocampus actively modulates food intake and energy metabolism, but direct evidence for the exact role of the hippocampus in modulating drinking behaviors is lacking. We observed decreased number of c-Fos-positive neurons in the ventral hippocampal CA1 (vCA1) after water restriction or hypertonic saline injection in rats. Suppressed vCA1 neuronal activities under the hypertonic state were further confirmed with in vivo electrophysiological recording, and the level of suppression paralleled both the duration and the total amount of water consumption. Chemogenetic inhibition of vCA1 pyramidal neurons increased water consumption in rats injected with both normal and hypertonic saline. These findings suggest that suppression of vCA1 pyramidal neuronal activities enhances water intake.

Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst.

Neuroimaging studies have shown that the anterior cingulate cortex (ACC) is consistently activated by thirst and may underlie the affective motivation of drinking behaviour demanded by thirst. But direct evidence for this hypothesis is lacking. The present study evaluated potential correlations between ACC neuronal activity and drinking behaviour in rats injected with different concentrations of saline. We observed an increased number of c-Fos-positive neurons in the ACC after injection of hypertonic saline, indicating strong ACC neuronal activation under hyperosmotic thirst. Increased firing rates of putative ACC pyramidal neurons preceded drinking behaviour and positively correlated with both the total duration of drinking and the total amount of water consumed. Chemogenetic inhibition of ACC pyramidal neurons changed drinking behaviour from an explosive and short-lasting pattern to a gradual but more persistent pattern, without affecting either the total duration of drinking or the total amount of water consumed. Together, these findings support a role of the ACC in modulating the affective-motivative dimension of hyperosmolality-induced thirst.

Adult Hippocampal Neurogenesis along the Dorsoventral Axis Contributes Differentially to Environmental Enrichment Combined with Voluntary Exercise in Alleviating Chronic Inflammatory Pain in Mice.

Cognitive behavioral therapy, such as environmental enrichment combined with voluntary exercise (EE-VEx), is under active investigation as an adjunct to pharmaceutical treatment for chronic pain. However, the effectiveness and underlying mechanisms of EE-VEx remain unclear. In mice with intraplantar injection of complete Freund's adjuvant, our results revealed that EE-VEx alleviated perceptual, affective, and cognitive dimensions of chronic inflammatory pain. These effects of EE-VEx on chronic pain were contingent on the occurrence of adult neurogenesis in the dentate gyrus in a functionally dissociated manner along the dorsoventral axis: neurogenesis in the ventral dentate gyrus participated in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas neurogenesis in the dorsal dentate gyrus was involved in EE-VEx's cognitive-enhancing effects. Chronic inflammatory pain was accompanied by decreased levels of brain-derived neurotrophic factor (BDNF) in the dentate gyrus, which were reversed by EE-VEx. Overexpression of BDNF in the dentate gyrus mimicked the effects of EE-VEx. Our results demonstrate distinct contribution of adult hippocampal neurogenesis along the dorsoventral axis to EE-VEx's beneficial effects on different dimensions of chronic pain.SIGNIFICANCE STATEMENT Environmental enrichment combined with voluntary exercise (EE-VEx) is under active investigation as an adjunct to pharmaceutical treatment for chronic pain, but its effectiveness and underlying mechanisms remain unclear. In a mouse model of inflammatory pain, the present study demonstrates that the beneficial effects of EE-VEx on chronic pain depend on adult neurogenesis with a dorsoventral dissociation along the hippocampal axis. Adult neurogenesis in the ventral dentate gyrus participates in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas that in the dorsal pole is involved in EE-VEx's cognitive-enhancing effects in chronic pain.

Increased expression of CaV3.2 T-type calcium channels in damaged DRG neurons contributes to neuropathic pain in rats with spared nerve injury.

Ion channels are very important in the peripheral sensitization in neuropathic pain. Our present study aims to investigate the possible contribution of CaV3.2 T-type calcium channels in damaged dorsal root ganglion neurons in neuropathic pain. We established a neuropathic pain model of rats with spared nerve injury. In these model rats, it was easy to distinguish damaged dorsal root ganglion neurons (of tibial nerve and common peroneal nerve) from intact dorsal root ganglion neurons (of sural nerves). Our results showed that CaV3.2 protein expression increased in medium-sized neurons from the damaged dorsal root ganglions but not in the intact ones. With whole cell patch clamp recording technique, it was found that after-depolarizing amplitudes of the damaged medium-sized dorsal root ganglion neurons increased significantly at membrane potentials of -85 mV and -95 mV. These results indicate a functional up-regulation of CaV3.2 T-type calcium channels in the damaged medium-sized neurons after spared nerve injury. Behaviorally, blockade of CaV3.2 with antisense oligodeoxynucleotides could significantly reverse mechanical allodynia. These results suggest that CaV3.2 T-type calcium channels in damaged medium-sized dorsal root ganglion neurons might contribute to neuropathic pain after peripheral nerve injury.

Anxiolytic effects of hippocampal neurosteroids in normal and neuropathic rats with spared nerve injury.

Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAA receptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests. We observed increased levels of hippocampal neurosteroids (pregnenolone, progesterone, deoxycorticosterone, and allopregnanolone) in rats with chronic neuropathic pain (28 days after spared nerve injury). Meanwhile, the expression of the translocator protein, the upstream steroidogenesis rate-limiting enzyme, increased in the ventral but not dorsal hippocampus of neuropathic rats. In both naïve and neuropathic rats, in vivo stereotaxic microinjection of PK 11195, the translocator protein inhibitor, into the ventral hippocampus exacerbated anxiety-like behaviors. These results indicate anxiolytic effects of hippocampal neurosteroids in both normal and neuropathic rats. Neurosteroids could be considered as agents for treatment of general and pain-related anxiety disorders.

Incidence and risk factors for proximal junctional kyphosis: a meta-analysis.

PURPOSE: To analyse the incidence and risk factors associated with proximal junctional kyphosis (PJK) following spinal fusion, we collect relative statistics from the articles on PJK and perform a meta-analysis. METHODS: An extensive search of literature was performed in PubMed, Embase, and The Cochrane Library (up to April 2015). The following risk factors were extracted: age at surgery, gender, combined anterior-posterior surgery, use of pedicle screw at top of construct, hybrid instrumentation, thoracoplasty, fusion to sacrum (S1), preoperative thoracic kyphosis angle (T5-T12) >40°, bone mineral density (BMD) and preoperative to postoperative sagittal vertical axis (SVA difference) >5 cm. Data analysis was conducted with RevMan 5.3 and STATA 12.0. RESULTS: A total of 14 unique studies including 2215 patients were included in the final analyses. The pooled analysis showed that there were significant difference in age at surgery >55 years old (OR 2.19, 95 % CI 1.36-3.53, p = 0.001), fusion to S1 (OR 2.12, 95 % CI 1.57-2.87, p < 0.001), T5-T12 >40° (OR 2.68, 95 % CI 1.73-4.13, p < 0.001), low BMD (OR 2.37, 95 % CI 1.45-3.87, p < 0.001) and SVA difference >5 cm (OR 2.53, 95 % CI 1.24-5.18, p = 0.01). However, there was no significant difference in gender (OR 0.98, 95 % CI 0.74-1.30, p = 0.87), combined anterior-posterior surgery (OR 1.55, 95 % CI 0.98-2.46, p = 0.06), use of pedicle screw at top of construct (OR 1.55, 95 % CI 0.67-3.59, p = 0.30), hybrid instrumentation (OR 1.31, 95 % CI 0.92-1.87, p = 0.13) and thoracoplasty (OR 1.55, 95 % CI 0.89-2.72, p = 0.13). The incidence of PJK following spinal fusion was 30 % (ranged from 17 to 62 %) based on the 14 studies. CONCLUSIONS: The results of our meta-analysis suggest that age at surgery >55 years, fusion to S1, T5-T12 >40°, low BMD and SVA difference >5 cm are risk factors for PJK. However, gender, combined anterior-posterior surgery, use of pedicle screw at top of construct, hybrid instrumentation and thoracoplasty are not associated with PJK.

Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes.

Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.

Ventral Hippocampal CA1 Pyramidal Neurons Encode Nociceptive Information.

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.

Dynamic Changes of the Infralimbic Cortex and Its Regulation of the Prelimbic Cortex in Rats with Chronic Inflammatory Pain.

The prelimbic cortex (PL) is actively engaged in pain modulation. The infralimbic cortex (IL) has been reported to regulate the PL. However, how this regulation affects pain remains unclear. In the present study, we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli, but a temporary hypo-function of the IL by in vivo electrophysiological recording in rats with peripheral inflammation. Manipulation of the PL or IL had opposite effects on thermal hyperalgesia. Furthermore, the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL. Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia, whereas its inhibition exacerbated chronic pain. Overall, our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain: hypo-function of the IL leads to hyperactivity of the PL, which regulates thermal hyperalgesia, and thus contributes to the chronicity of pain.

[The mechanism of the glial cells involved in neuropathic pain].

Neuropathic pain is caused by lesion or disease of somatosensory system. The glial cell includes astrocyte and microglia in central nervous system (CNS), as well as satellite cell and Schwann cell in peripheral nervous system (PNS). Neural lesion activates the glial cell, inducing its morphology changes and certain protein expression. By interacting with neurons, the glial cell plays important roles in both the initiation and maintenance of neuropathic pain. In this review, we present recent progress in the study of glial mechanisms underlying neuropathic pain.

Relationship of Change in Cervical Curvature after Laminectomy with Lateral Mass Screw Fixation to Spinal Cord Shift and Clinical Efficacy.

BACKGROUND AND STUDY AIMS: Although laminectomy with lateral mass screw fixation (LCSF) is an effective surgical treatment for cervical spondylotic myelopathy (CSM), loss of cervical curvature may result. This study aimed to investigate the effect of cervical curvature on spinal cord drift distance and clinical efficacy. PATIENTS AND METHODS: We retrospectively analyzed 78 consecutive CSM patients with normal cervical curvature who underwent LCSF. Cervical curvature was measured according to Borden's method 6 months after surgery. Study patients were divided into two groups: group A, reduced cervical curvature (cervical lordosis depth 0-7mm; n = 42); and group B, normal cervical curvature (cervical lordosis depth 7-17mm; n = 36). Spinal cord drift distance, laminectomy width, neurologic functional recovery, axial symptom (AS) severity, and incidence of C5 palsy were measured and compared. RESULTS: Cervical lordosis depth was 5.1 ± 1.2 mm in group A and 12.3 ± 2.4 mm in group B (p < 0.05). Laminectomy width was 21.5 ± 2.6 mm in group A and 21.9 ± 2.8 mm in group B (p > 0.05). Spinal cord drift distance was significantly shorter in group A (1.9 ± 0.4 vs. 2.6 ± 0.7 mm; p < 0.05). The Japanese Orthopaedic Association (JOA) score significantly increased after surgery in both groups (p < 0.05). Neurologic recovery rate did not differ between the two groups (61.5 vs. 62.7%; p > 0.05). AS severity was significantly higher in group A (p < 0.05). C5 palsy occurred in three group A patients (7.1%) and four group B patients (11.1%), but the difference was not significant (p > 0.05). CONCLUSION: After LCSF, 53.8% of the patients developed loss of cervical curvature. A smaller cervical curvature resulted in a shorter spinal cord drift distance. Loss of cervical curvature was related to AS severity but not improvement of neurologic function or incidence of C5 palsy.

Improvement of 3-D Ultrasound Spine Imaging Technique Using Fast Reconstruction Algorithm.

Three-dimensional (3-D) freehand ultrasound (US) imaging has been applied to the investigation of spine deformity. However, it is a challenge for the current 3-D imaging reconstruction algorithms to achieve a balance between image quality and computation time. The objectives of this article are to implement a new fast reconstruction algorithm that can fulfill the request of immediate demonstration and processing for high-quality 3-D spine imaging, and to evaluate the reliability and accuracy of scoliotic curvature measurement when using the algorithm. The fast dot-projection (FDP) algorithm was applied for voxel-based nearest neighbor (VNN), multiple plane interpolation (MPI), and pixel nearest neighbor (PNN) protocols to reduce the reconstruction time. The 3-D image volume was reconstructed from the datasets acquired from scoliotic subjects. The computational cost, image characteristics, and statistical analyses of curve measurements were compared and evaluated among different reconstruction protocols. The results illustrated that the 3-D spine images using the FDP-MPI4 algorithm showed higher brightness (20%), contrast (14%), and signal-to-noise ratio (SNR) (26%) than FDP-VNN. The measurement performed by trainee rater exhibited significant improvement in measurement reliability and accuracy using FDP-MPI4 in comparison with FDP-VNN ( ), and the intraclass correlation coefficient (ICC) of interrater measurement increased from 0.88 to 0.96. The FDP-PNN method could acquire and reconstruct spine images simultaneously and present the results in 1-2 min, which showed the potential to provide the approximate real-time visualization for fast screening.

Automatic Hip Detection in Anteroposterior Pelvic Radiographs-A Labelless Practical Framework.

Automated detection of the region of interest (ROI) is a critical step in the two-step classification system in several medical image applications. However, key information such as model parameter selection, image annotation rules, and ROI confidence score are essential but usually not reported. In this study, we proposed a practical framework of ROI detection by analyzing hip joints seen on 7399 anteroposterior pelvic radiographs (PXR) from three diverse sources. We presented a deep learning-based ROI detection framework utilizing a single-shot multi-box detector with a customized head structure based on the characteristics of the obtained datasets. Our method achieved average intersection over union (IoU) = 0.8115, average confidence = 0.9812, and average precision with threshold IoU = 0.5 (AP50) = 0.9901 in the independent testing set, suggesting that the detected hip regions appropriately covered the main features of the hip joints. The proposed approach featured flexible loose-fitting labeling, customized model design, and heterogeneous data testing. We demonstrated the feasibility of training a robust hip region detector for PXRs. This practical framework has a promising potential for a wide range of medical image applications.

Modified extrapedicular kyphoplasty for the treatment of lumbar compression fracture: Case report and technical note.

RATIONALE: Traditionally, transpedicular approach was used in the treatment of osteoporotic lumbar compression fracture. In order to avoid the risks of pedicle disruption and spinal canal intrusion, extrapedicular approache has been attempted. The aim of the article is to present the modified extrapedicular kyphoplasty technique for the treatment of osteoporotic lumbar compression fracture. PATIENT CONCERNS: A 62-year-old woman suffered from severe low back pain after an accidental fall 10 days ago. Low back pain was obvious when turning over and getting out of bed. It was not relieved after bed rest and conservative treatment. Visual analog scale (VAS) of low back pain was 8 points and Oswestry disability index score was 80%. DIAGNOSIS: Magnetic resonance imaging showed osteoporotic vertebral compression fracture of L2 and L3. INTERVENTIONS: We performed modified extrapedicular kyphoplasty for the patient. The technique has a standardized operating procedure. The puncture point of skin is determined according to preoperative computer tomography and X-ray. The puncture point of vertebral body is located at the outer upper edge of the pedicle. The puncture direction is from the upper edge of the pedicle to the lower edge of the contralateral pedicle. OUTCOMES: The operation time was 20 minutes. The intraoperative blood loss was 5 mL. The amount of bone cement was 4 mL in L2 and 5 mL in L3. VAS of low back pain was 2 points in 1 day after surgery. Preoperative symptoms were significantly improved. LESSONS: Modified extrapedicular kyphoplasty is a safe and effective technique for the treatment of osteoporotic lumbar compression fracture, which should be promoted and applied.

Modified grade 4 osteotomy for the correction of post-traumatic thoracolumbar kyphosis: A retrospective study of 42 patients.

Many surgical procedures have been developed for the treatment of post-traumatic thoracolumbar kyphosis. But there is a significant controversy over the ideal management. The aim of this study was to illustrate the technique of modified grade 4 osteotomy for the treatment of post-traumatic thoracolumbar kyphosis and to evaluate clinical and radiographic results of patients treated with this technique.From May 2013 to May 2018, 42 consecutive patients experiencing post-traumatic thoracolumbar kyphosis underwent the technique of modified grade 4 osteotomy, and their medical records were retrospectively collected. Preoperative and postoperative sagittal Cobb angle, visual analog scale (VAS), Oswestry disability index (ODI), and American Spinal Injury Association (ASIA) were recorded. The average follow-up period was 29.7 ±â€Š14.2 months.The operation time was 185.5 ±â€Š26.8 minutes, the intraoperative blood loss was 545.2 ±â€Š150.1 mL. The Cobb angles decreased from 38.5 ±â€Š3.8 degree preoperatively to 4.2 ±â€Š2.6 degree 2 weeks after surgery (P < .001). The VAS reduced from 6.5 ±â€Š1.1 preoperatively to 1.5 ±â€Š0.9 at final follow-up (P < .001), and the ODI reduced from 59.5 ±â€Š15.7 preoperatively to 15.9 ±â€Š5.8 at final follow-up (P < .001). Kyphotic deformity was successfully corrected and bony fusion was achieved in all patients. Neurologic function of 7 cases was improved to various degrees.Modified grade 4 osteotomy, upper disc, and upper one-third to half of pedicle are resected, is an effective treatment option for post-traumatic thoracolumbar kyphosis. However, the long-term clinical effect still needs further studies.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies: Characterization by Single-Unit Recording in Rats.

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aß and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aß fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.

Development of a CRISPR-SaCas9 system for projection- and function-specific gene editing in the rat brain.

A genome editing technique based on the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 enables efficient modification of genes in various cell types, including neurons. However, neuronal ensembles even in the same brain region are not anatomically or functionally uniform but divide into distinct subpopulations. Such heterogeneity requires gene editing in specific neuronal populations. We developed a CRISPR-SaCas9 system-based technique, and its combined application with anterograde/retrograde AAV vectors and activity-dependent cell-labeling techniques achieved projection- and function-specific gene editing in the rat brain. As a proof-of-principle application, we knocked down the cbp (CREB-binding protein), a sample target gene, in specific neuronal subpopulations in the medial prefrontal cortex, and demonstrated the significance of the projection- and function-specific CRISPR-SaCas9 system in revealing neuronal and circuit basis of memory. The high efficiency and specificity of our projection- and function-specific CRISPR-SaCas9 system could be widely applied in neural circuitry studies.

A Novel 3D-Printed Multi-Drive System for Synchronous Electrophysiological Recording in Multiple Brain Regions.

Extracellular electrophysiology has been widely applied in neural network studies. Local field potentials and single-unit activities can be recorded with high-density electrodes, which facilitate the decoding of neural codes. However, the chronic multi-regional recording is still a challenging task for achieving high placement accuracy and long-term stability. Here, we present a novel electrode design with low-cost 3D-printed parts and custom printed circuits boards. This new design could facilitate precise electrode placement in multiple brain regions simultaneously and reduce the working time for surgical procedures as well. In this paper, the design and fabrication of the 3D printed multi-channel microdrive are explained in detail. We also show the result of high-quality electrophysiological recordings in eight pain-related areas from rats and the electrode placement accuracy. This novel 3D-printed multi-drive system could achieve synchronous electrophysiological recording in multiple brain regions and facilitate future neural network research.