Attending the virtual FENS 2020 meeting? Make sure to visit our virtual booths! Below you can find a sampling of products we will be showcasing along with a sample of relevant publications citing their use in neuroscience research.
Electrophysiology
HEKA, Multi Channel Systems, and Warner Instruments provide solutions for all areas of electrophysiology including patch clamp, array based extracellular recordings in vitro, recording and stimulation in vivo, Ussing systems, planar lipid bilayer, and scanning probe microscopy.
Patch Clamp
Neurexins cluster Ca2+ channels within the presynaptic active zone
Neurexin, a presynaptic adhesion molecule, has a central role in shaping synapse properties. However, their role in Ca2+ channel gating or trafficking is so far almost unknown. To better understand this role, the research team used conditional knock-out mice with cell-specific neurexin 1/2/3 deletion at the Calyx of Held synapse in the mouse auditory brainstem. They showed that the neurexin-deletion does not affect synapse development but impaired the fast neurotransmitter release. Further, the neurexins seem to be essential for organizing the tight spatial coupling of Ca2+ channels to release sites of the Calyx of Held. The team conducted patch-clamp recordings using HEKA’s EPC 10 USB patch clamp amplifier and measured capacitance using PATCHMASTER software.1
Array Based Extracellular Recordings
Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices
This study investigates the effects of using human cerebrospinal fluid (hCSF) instead of artificial cerebrospinal fluid (aCSF) for electrophysiological recordings. Combining the advantages of high-resolution electrode arrays from Multi Channel Systems, both with conventional metal electrodes as well as CMOS sensors, with human tissue slices, the research team describe the activity changes observed in cortical and hippocampal networks. Due to the high-resolution data acquired with the multielectrode arrays (MEAs), they were able to show changes not only on a network scale but also down to on the level of subpopulations of neuronal ensembles. As the authors point out, these findings should be considered when trying to establish in vitro models for human physiology or disease.2
Neuronal Imaging
Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors
Previous studies have suggested that gastrin-releasing peptide (GRP) is a principal neuropeptide for transmitting non-histaminergic itch from primary afferents to GRP-receptor (GRPR) neurons in the spinal cord dorsal horn. GRP fiber activation by optogenetics and chemogenetics is known to evoke itch-related scratching behavior. In this study, the authors generated and validated a knock-in/knockout (floxed) mouse model to investigate the role of GRP neurons in itch and pain. To validate the expression of transformed GRPR neurons, primary neuronal culture was harvested and plated on coverslips and imaged on a Nikon microscope using a Warner Instruments RC-26G diamond bath imaging and recording chamber. The authors successfully established the role of GRP as an itch-specific neuropeptide in transmitting non-histaminergic itch. They also showed that spinal GRP neurons are dispensable for itch and pain transmission. These author's newly generated mouse line(s) offer unprecedented access to the GRP-GRPR system for unraveling the coding logic of itch.3
Fluidics
Harvard Apparatus syringe pumps are suitable for a wide range of applications including neuroscience, mass spec calibration, drug and nutritional studies, macro to micro reactors, electrospinning, and microfluidics.
Exploring the Biomechanical Properties of Brain Malignancies and Their Pathologic Determinants In Vivo with Magnetic Resonance Elastography
Malignant tumors are typically associated with altered rigidity relative to normal host tissue. Magnetic resonance elastography (MRE) enables the noninvasive quantitation of the mechanical properties of deep-seated tissue following application of an external vibrational mechanical stress to that tissue. In this preclinical study, researchers used MRE to quantify the elasticity modulus and viscosity modulus of three intracranially implanted glioma and breast metastatic tumor models. In all these brain tumors, the researchers found a notable softness characterized by lower elasticity and viscosity than normal brain parenchyma, enabling their detection on elasticity and viscosity parametric maps. The Harvard Apparatus Pump 11 Elite Nanomite was used to precisely inject the tumor cell suspension in the critical areas of the subject’s brain for tumor establishment.4
Increasing the effectiveness of intracerebral injections in adult and neonatal mice: a neurosurgical point of view
Intracerebral injections of tracers or viral constructs in rodents are now commonly used in the neurosciences and must be executed perfectly. The purpose of this research is to update existing protocols for intracerebral injections in adult and neonatal mice. The described procedure for stereotaxic injections in adult mice allows the investigator to improve the effectiveness and safety and save time. The research found that this updated protocol allowed stereotaxic injections in adult mice to be performed in 20 min and have >90% efficacy in targeting the injection site. Injections in neonatal mice can be performed in 5 min. The Harvard Apparatus Pump 11 Elite Nanomite was used as the infusion pump to test the updated protocol.5
A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip
Studies of neonatal neural pathologies and development of appropriate therapeutics are hampered by a lack of relevant in vitro models of neonatal blood-brain barrier (BBB). To establish such a model, the researchers have developed a novel blood-brain barrier on a chip (B3C) that comprises a tissue compartment and vascular channels placed side-by-side mimicking the three-dimensional morphology, size and flow characteristics of microvessels in vivo. This model offers an additional tool in the study of neonatal blood brain barrier function as well as screening of novel therapeutics. The Harvard Apparatus PHD ULTRA™ syringe pump was used to provide the simulated vascular flow and was also used to inject a cell suspension into the tissue compartment of the B3C.6
Behavioral Assessment
Panlab and Coulbourn Instruments are industry leading developers and manufacturers of solutions for behavioral neuroscience research in small laboratory animals. Applications include basic science, phenotyping, and drug discovery/screening with solutions such as activity wheels, treadmills, mazes, rotarods, grip tests, tail shock, operant conditioning, and video tracking software. Behavioral examination can be combined with DSI’s implantable telemetry for a more comprehensive study.
Fear Conditioning
Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice
This study examines the role dysregulation of GABA neurons plays in the development of epilepsy and the role of phospholipase Cγ1, in seizure generation. The team deleted phospholipase Cγ1 in the GABA neurons of older mice and saw handling-induced seizures, hypoactivity, reduced anxiety, and fear memory deficit. They used Panlab’s SMART video tracking software to monitor behavior and their fear conditioning chamber to deliver foot shocks and evaluate fear memory. In addition, DSI implantable telemetry was used to measure EEG for seizure detection.7
Locomotor Activity
Does Exposure to a Radiofrequency Electromagnetic Field Modify Thermal Preference in Juvenile Rats?
Many people who live near mobile phone base stations report sleep disturbances, and this research team previously showed that chronic exposure to a low intensity radiofrequency electromagnetic field (RF-EMF) may cause fragmentations in paradoxical sleep. This study was intended to determine if thermoregulatory processes may play a role in sleep disturbance. The research team used DSI implantable telemetry to record sleep through EEG and EMG measurements. They also used an infrared activity monitor from Coulbourn Instruments to measure locomotor activity within environmental chambers. The study’s results indicate subjects prefer higher sleeping temperatures after exposure to RM-EMF, possibly a result of a cold thermal sensation.8
Voluntary and Forced Exercise
Changes in Heart Rate and Its Regulation by the Autonomic Nervous System Do Not Differ Between Forced and Voluntary Exercise in Mice
This study aimed to compare the utility of forced and voluntary exercise in research, as forced exercise introduces stress to the data. They compared the effects of both forms of exercise on cardiovascular function and heart rate regulation by the autonomic nervous system. Panlab’s treadmill and Coulbourn’s running wheel were used for forced and voluntary exercise. Collecting an ECG signal from a DSI implantable telemetry device, heart rate and heart rate variability data were calculated. Results show that both forced and voluntary exercise result in comparable physiological remodeling, heart rate reductions, and heart rate-independent enhancements of heart rate variability.9
Physiologic Monitoring
Data Sciences International is the recognized global leader in physiologic monitoring, offering telemetry, respiratory and inhalation solutions, instrumentation, software, and services that serve applications spanning basic research to drug development. Specific to neuroscience, DSI enables researchers to measure endpoints such as EEG, EMG, temperature, activity, and more using implantable telemetry. DSI’s Buxco line of products allow measurement of respiratory endpoints include tidal/minute volume, resistance, compliance, and more. The Buxco whole body plethysmography chambers can be adapted to allow integration of optogenetics, fluid swivels, or tethered biopotential collection. In addition, non-DSI signals, including behavioral assessment, can be collected and synchronized in Ponemah software using the Signal Interface, enabling more comprehensive studies.
Video-EEG
Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy
Cardiac rhythm disturbances, such as changes in heart rate or arrhythmias, caused by seizures can increase risk of sudden unexpected death in epilepsy (SUDEP). This study prescribed a technique to study abnormal brain and cardiac rhythms in which EEG and ECG are measured simultaneously while video is recorded to monitor the animals’ behavior. This study utilized techniques to collect EEC and ECG using DSI’s tethered 12-channel biopotential pod. Video monitoring was synchronized to physiologic data using the Ponemah software platform. The study also describes methods for analyzing seizure, EEG spectral power, cardiac function, and heart rate variability data and shows that video-EEG-ECG monitoring in mouse models of epilepsy is a powerful tool for detecting neurological, cardiovascular, or brain-heart interaction dysfunction.10
Telemetry Video-Electroencephalography (EEG) in Rats, Dogs and Non-Human Primates: Methods in Follow-Up Safety Pharmacology Seizure Liability Assessments
This study outlines a method for conducting seizure liability studies in safety pharmacology. Researchers at CiToxLAB (now Charles River Laboratories) characterized and compared seizure liability in rats, beagle dogs, and cynomolgus primates using a Video-EEG approach. They measured EEG in all three species using DSI implantable telemetry and used video monitoring for seizure confirmation. Although rats serve as a first-line model and beagles have a high susceptibility to seizure, non-human primates are critical in these studies due to their resemblance and translational potential to humans.11
Respiratory Integration
Neuron-specific Kv1.1 deficiency is sufficient to cause epilepsy, premature death, and cardiorespiratory dysregulation
This study examined the cardiovascular, respiratory, and neurological events associated with SUDEP. Specifically, they assessed cardiac arrhythmias caused by seizure by deleting Kcna1, a gene expressed in both the brain and heart associated with SUPEP, in the neurons of conditional knockout mice. They wanted to see if deletion in the brain would be enough to stop arrhythmias or if deletion in the heart would also be required. Throughout this study, the team measured ECG to calculate heart rate variability and look at arrhythmias, EEG, respiratory rate, tidal volume, and minute volume using DSI’s whole body plethysmograph chambers integrated with electrical commutators for tethered biopotential collection. They also used video monitoring for seizure detection and confirmation. All data was compiled and synchronized using Ponemah software. The study indicates disturbed diurnal HRV patterns as a SUDEP biomarker and shows an increased risk of death due to brain mechanisms even if the heart is not compromised.12
If you will not be attending the virtual FENS meeting or would like to discuss your research sooner, please feel free to contact us using the methods below:
Electrophysiology
Fluidics and Behavioral Assessment
Physiologic Monitoring
References
1Luo F, Sclip A, Jiang M, Südhof TC. (2020). “Neurexins cluster Ca2+ channels within the presynaptic active zone”. The EMBO Journal, 39: e103208. https://doi.org/10.15252/embj.2019103208.
2Wickham J, Corna A, Schwarz N, et. al. (2020). “Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices”. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2020.00283.
3Barry, DM, Liu, X, Liu, B, et al. (2020). “Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors”. Nature Communications, 11:1397. https://doi.org/10.1038/s41467-020-15230-y.
4Jamin Y, Boult JKR, Li J. (2015). "Exploring the Biomechanical Properties of Brain Malignancies and Their Pathologic Determinants In Vivo with Magnetic Resonance Elastography". Cancer Research, 75(7). https://doi.org/10.1158/0008-5472.CAN-14-1997.
5Mathon B, Nassar M, Simonnet J. (2015). "Increasing the effectiveness of intracerebral injections in adult and neonatal mice: a neurosurgical point of view". Neuroscience Bulletin, 31(6): 685-696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563725/pdf/12264_2015_Article_1558.pdf
6Deosarkar SP, Prabhakarpandian B, Wang B, Sheffield JB, B Krynska, Kiani MF. (2015). "A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip". PLoS One, 10(11): e0142725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640840/
8Pelletier A, Delanaud S, de Seze R, et. al. (2014). “Does Exposure to a Radiofrequency Electromagnetic Field Modify Thermal Preference in Juvenile Rats?”. PLoS One, 9(6): e99007. https://dx.doi.org/10.1371%2Fjournal.pone.0099007.
9Lakin R, Guzman C, Izaddoustdar F, Polidovitch N, Goodman JM, Back PHx. (2018). “Changes in Heart Rate and Its Regulation by the Autonomic Nervous System Do Not Differ Between Forced and Voluntary Exercise in Mice”. Frontiers in Physiology, 9: 841. https://dx.doi.org/10.3389%2Ffphys.2018.00841.
10Mishra V, Gautier NM, Glasscock E. (2018). “Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy”. JoVE, 131. http://dx.doi.org/10.3791/57300.
11Bassett L, Troncy E, Pouliot M, Paquette D, Ascah A, Authier S. (2014). “Telemetry Video-Electroencephalography (EEG) in Rats, Dogs and Non-Human Primates: Methods in Follow-Up Safety Pharmacology Seizure Liability Assessments”. Journal of Pharmacological and Toxicological Methods, 70:3. https://doi.org/10.1016/j.vascn.2014.07.005.
12Trosclair K, Dhaibar HA, Gautiera NM, Mishra V, Glasscock E. (2020). “Neuron-specific Kv1.1 deficiency is sufficient to cause epilepsy, premature death, and cardiorespiratory dysregulation”. Neurobiology of Disease, 137. https://doi.org/10.1016/j.nbd.2020.104759.