Rat Motor Cortex Research Articles

Correlation between Spike Potential and Field Potential in the Motor Cortex of Rats with Parkinson’s Disease

Correlation between the spike discharge and rhythm of local field potential (LFP) of neurons provides clues on the information coded by the nerves. In this study, spike and LFP in the motor cortex (M1) of rats with Parkinson’s diseases (PD) at the inattentive rest and during walking along a ladder were recorded using multi-channel neuronal recording system (Plexon). Neuronal classification was first performed for the nuclei of M1. Then for different types of neurons, the spike-LFP correlation was analyzed in the M1 using three indicators, namely, coherence value, phase locking and spike-field coherence (SFC). Results: 1. Based on electrophysiological characteristics, the nuclei neurons in M1 were classified into two types respectively; 2. There was no significant difference in spike-LFP correlation in PD rats compared with the controls when at the inattentive rest; 3. There were different changes in the spike-LFP relationship for the PD rats compared with the controls when walking the ladders. The intensity of spike-LFP correlation decreased for type A neurons in M1, while it increased for type B neurons in M1.

Amorphous silicon carbide ultramicroelectrode arrays for neural stimulation and recording

Objective. Foreign body response to indwelling cortical microelectrodes limits the reliability of neural stimulation and recording, particularly for extended chronic applications in behaving animals. The extent to which this response compromises the chronic stability of neural devices depends on many factors including the materials used in the electrode construction, the size, and geometry of the indwelling structure. Here, we report on the development of microelectrode arrays (MEAs) based on amorphous silicon carbide (a-SiC). Approach. This technology utilizes a-SiC for its chronic stability and employs semiconductor manufacturing processes to create MEAs with small shank dimensions. The a-SiC films were deposited by plasma enhanced chemical vapor deposition and patterned by thin-film photolithographic techniques. To improve stimulation and recording capabilities with small contact areas, we investigated low impedance coatings on the electrode sites. The assembled devices were characterized in phosphate buffered saline for their electrochemical properties. Main results. MEAs utilizing a-SiC as both the primary structural element and encapsulation were fabricated successfully. These a-SiC MEAs had 16 penetrating shanks. Each shank has a cross-sectional area less than 60 µm2 and electrode sites with a geometric surface area varying from 20 to 200 µm2. Electrode coatings of TiN and SIROF reduced 1 kHz electrode impedance to less than 100 kΩ from ~2.8 MΩ for 100 µm2 Au electrode sites and increased the charge injection capacities to values greater than 3 mC cm−2. Finally, we demonstrated functionality by recording neural activity from basal ganglia nucleus of Zebra Finches and motor cortex of rat. Significance. The a-SiC MEAs provide a significant advancement in the development of microelectrodes that over the years has relied on silicon platforms for device manufacture. These flexible a-SiC MEAs have the potential for decreased tissue damage and reduced foreign body response. The technique is promising and has potential for clinical translation and large scale manufacturing.

Peripheral nerve stimulation can explain tACS effects in the rat motor cortex

Event Abstract Back to Event Peripheral nerve stimulation can explain tACS effects in the rat motor cortex Boateng Asamoah1*, Ahmad Khatoun1 and Myles McLaughlin1 1 Department of Neurosciences, KU Leuven, Belgium Introduction In transcranial alternating current stimulation (tACS) a sinusoid current is applied to scalp electrodes. As the current passes through the various tissues (scalp, skull, CSF and brain) the generated electric field goes from relatively strong in the scalp to very weak in the brain. It is thought that this weak field then modulates membrane potential and entrains neuronal spike timing. This is the assumed underlying mechanism of behavioural effects in humans as shown by various studies. However, this view has been challenged. Recent animal experiment and human head modelling studies show that the cortical field may be too weak to cause entrainment of spike timing. We term these conflicting results the ‘tACS paradox’. Aims To resolve the paradox we hypothesised that the relatively strong electric field generated in the scalp stimulates peripheral nerves which then give rhythmic input to the brain and cause neural entrainment. We tested this hypothesis in a rat model by separating the two possible mechanisms - namely transcranial (according to the existing view) and transcutaneous (according to our hypothesis). Methods In an anaesthetised rat we blocked the transcutaneous mechanism by stimulating directly on the dry skull while recording single neuron activity in the motor cortex. We then blocked the transcranial mechanism by stimulating the skin of a limb while recording from the same neurons. Results An electric field strength of around 1 V/m was need to cause neural entrainment with transcranial stimulation. Interestingly, transcutaneous stimulation with 1 mA currents also caused a similar amount of neural entrainment. Conclusions Both transcranial and transcutaneous stimulation can cause entrainment. Noticeably, the electric field strength needed to cause transcranial entrainment of rat motor cortex neurons is larger than is reached in human studies. Our results may help resolve the tACS paradox. Further experiments in humans are needed to test this hypothesis. Popular summary Transcranial electric stimulation is a promising technique where the head is stimulated with a low amplitude current. Various studies show that this technique can improve memory, motor and auditory function. However, the mechanism by which this works is not clear. In this study we used alternating (in the form of a sinewave) current to stimulate the skin of rats. Our results show that, at least in rats, the underlying mechanism of transcranial electric stimulation is the stimulation of nerves in the skin. Further experiments in humans should clarify whether this is also the case in humans. Acknowledgements This work was supported by: KU Leuven Research Funding STG/14/024 and EGM-D2929-C24/17/091. EIT Health Innovation by Ideas, NEURO-WEAR Project. Boateng Asamoah is SB PhD fellow at FWO Keywords: Science, tACS (transcranial alternating current stimulation), Rat motor cortex, Electric field strength, peripheral nerve stimulation, sensorimotor cortex, Spike time entrainment Conference: Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018. Presentation Type: e-posters Topic: NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE Citation: Asamoah B, Khatoun A and McLaughlin M (2019). Peripheral nerve stimulation can explain tACS effects in the rat motor cortex. Front. Neurosci. Conference Abstract: Belgian Brain Congress 2018 — Belgian Brain Council. doi: 10.3389/conf.fnins.2018.95.00079 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Aug 2018; Published Online: 17 Jan 2019. * Correspondence: Mr. Boateng Asamoah, Department of Neurosciences, KU Leuven, Leuven, 3000, Belgium, boateng.asamoah@kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Boateng Asamoah Ahmad Khatoun Myles McLaughlin Google Boateng Asamoah Ahmad Khatoun Myles McLaughlin Google Scholar Boateng Asamoah Ahmad Khatoun Myles McLaughlin PubMed Boateng Asamoah Ahmad Khatoun Myles McLaughlin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

In vivo Use of Dextran-based Anterograde Cortical Tracers to Assess the Integrity of the Cortical Spinal Tract.

When injected into the motor cortex of rats, anterograde tracers label fibers of the associated descending corticospinal tract (CST) that originate from pyramidal neurons in the tracer-injected cortex. These fibers can be assessed at the level of the spinal cord to determine the integrity of the descending CST and the spatial distribution of axons in the spinal grey matter. Here we provide detailed methods on the minimally invasive stereotaxic injection of anterograde tracers into the forelimb sensorimotor representation in the rat cortex. In addition, we detail the fixing and processing of spinal tissue for assessment of CST integrity and branching into spinal grey matter.

The Effects of De-Whiskering and Congenital Hypothyroidism on The Development of Nitrergic Neurons in Rat Primary Somatosensory and Motor Cortices.

Objective The aim of the present study is to investigate the effects of chronic whisker deprivation on possible alterations to the development of nitrergic neurons in the whisker part of the somatosensory (wS1) and motor (wM1) cortices in offspring with congenital hypothyroidism (CH). Materials and Methods In the experimental study, CH was induced by adding propylthiouracil to the rats drinking water from embryonic day 16 to postnatal day (PND) 60. In whisker-deprived (WD) pups, all the whiskers were trimmed from PND 1 to 60. Nitrergic interneurons in the wS1/M1 cortices were detected by NADPH-diaphorase histochemistry staining technique in the control (Ctl), Ctl+WD, Hypo and Hypo+WD groups. Results In both wS1 and wM1 cortices the number of nitrergic neurons was significantly reduced in the Hypo and Hypo+WD groups compared to Ctl and Ctl+WD groups, respectively (P<0.05) while bilateral whisker deprivation had no remarkable effect. The mean soma diameter size of NADPH-d labeled neurons in the Ctl+WD and Hypo+WD groups was decreased compared to the Ctl and Hypo groups, respectively. A similar patterns of decreased NADPH-d labeled neurons in the wS1/M1 cortices occur in the processes of nitrergic neurons in both congenital hypothyroidism and whisker deprivation. ConclusionOur results suggest that both congenital hypothyroidism and whisker deprivation may disturb normal development of the wS1 and wM1 cortical circuits in which nitrergic neurons are involved.

Comparison of Electrical and Ultrasound Neurostimulation in Rat Motor Cortex

Ultrasound (US) is known to non-invasively stimulate and modulate brain function; however, the mechanism of action is poorly understood. This study tested US stimulation of rat motor cortex (100 W/cm2, 200 kHz) in combination with epidural cortical stimulation. US directly evoked hindlimb movement. This response occurred even with short US bursts (3 ms) and had short latency (10 ms) and long refractory (3 s) periods. Unexpectedly, the epidural cortical stimulation hindlimb response was not altered during the 3-s refractory period of the US hindlimb response. This finding suggests that the US refractory period is not a general suppression of motor cortex, but rather the recovery time of a US-specific mechanism.

Posterior Thalamic Nucleus Modulation of Tactile Stimuli Processing in Rat Motor and Primary Somatosensory Cortices.

Rodents move rhythmically their facial whiskers and compute differences between signals predicted and those resulting from the movement to infer information about objects near their head. These computations are carried out by a large network of forebrain structures that includes the thalamus and the primary somatosensory (S1BF) and motor (M1wk) cortices. Spatially and temporally precise mechanorreceptive whisker information reaches the S1BF cortex via the ventroposterior medial thalamic nucleus (VPM). Other whisker-related information may reach both M1wk and S1BF via the axons from the posterior thalamic nucleus (Po). However, Po axons may convey, in addition to direct sensory signals, the dynamic output of computations between whisker signals and descending motor commands. It has been proposed that this input may be relevant for adjusting cortical responses to predicted vs. unpredicted whisker signals, but the effects of Po input on M1wk and S1BF function have not been directly tested or compared in vivo. Here, using electrophysiology, optogenetics and pharmacological tools, we compared in adult rats M1wk and S1BF in vivo responses in the whisker areas of the motor and primary somatosensory cortices to passive multi-whisker deflection, their dependence on Po activity, and their changes after a brief intense activation of Po axons. We report that the latencies of the first component of tactile-evoked local field potentials in M1wk and S1BF are similar. The evoked potentials decrease markedly in M1wk, but not in S1BF, by injection in Po of the GABAA agonist muscimol. A brief high-frequency electrical stimulation of Po decreases the responsivity of M1wk and S1BF cells to subsequent whisker stimulation. This effect is prevented by the local application of omega-agatoxin, suggesting that it may in part depend on GABA release by fast-spiking parvalbumin (PV)-expressing cortical interneurons. Local optogenetic activation of Po synapses in different cortical layers also diminishes M1wk and S1BF responses. This effect is most pronounced in the superficial layers of both areas, known to be the main source and target of their reciprocal cortico-cortical connections.

Simultaneously Excitatory and Inhibitory Effects of Transcranial Alternating Current Stimulation Revealed Using Selective Pulse-Train Stimulation in the Rat Motor Cortex.

Transcranial alternating current stimulation (tACS) uses sinusoidal, subthreshold, electric fields to modulate cortical processing. Cortical processing depends on a fine balance between excitation and inhibition and tACS acts on both excitatory and inhibitory cortical neurons. Given this, it is not clear whether tACS should increase or decrease cortical excitability. We investigated this using transcranial current stimulation of the rat (all males) motor cortex consisting of a continuous subthreshold sine wave with short bursts of suprathreshold pulse-trains inserted at different phases to probe cortical excitability. We found that when a low-rate, long-duration, suprathreshold pulse-train was used, subthreshold cathodal tACS decreased cortical excitability and anodal tACS increased excitability. However, when a high-rate, short-duration, suprathreshold pulse-train was used this pattern was inverted. An integrate-and-fire model incorporating biophysical differences between cortical excitatory and inhibitory neurons could predict the experimental data and helped interpret these results. The model indicated that low-rate suprathreshold pulse-trains preferentially stimulate excitatory cortical neurons, whereas high-rate suprathreshold pulse-trains stimulate both excitatory and inhibitory neurons. If correct, this indicates that suprathreshold pulse-train stimulation may be able to selectively control the excitation-inhibition balance within a cortical network. The excitation-inhibition balance then likely plays an important role in determining whether subthreshold tACS will increase or decrease cortical excitability.SIGNIFICANCE STATEMENT Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that uses weak sinusoidal electric fields to modulate cortical activity. In healthy volunteers tACS can modulate perception, cognition, and motor function but the underlying neural mechanism is poorly understood. In this study, using rat motor cortex, we found that tACS effects are highly variable: applying the same tACS waveform to the same cortical area does not always give the same change in cortical excitability. An integrate-and-fire model incorporating excitatory pyramidal and inhibitory interneurons indicated that tACS effects likely depend on the cortical excitation-inhibition balance. When cortical activity is excitation dominated one particular tACS phase increases excitability, but when the cortical activity is inhibition dominated the same tACS phase actually decreases excitability.

Widespread functional opsin transduction in the rat cortex via convection-enhanced delivery optimized for horizontal spread

BackgroundWidespread opsin expression in the cortex of rats, where transgenic models have not been established, is not practical to achieve with the traditional diffusion-based virus transduction methods (DBD). New methodWe developed protocols for convection-enhanced delivery (CED) of virus for optogenetic transduction of the rat cortex. Targeting the motor forelimb area as an example, we performed dual-site CED (6μL of virus per site, 3mm pitch between sites) in the rat motor cortex. ResultsWe identified injection parameters optimized for horizontal spread of infusate in the agarose gel model and then demonstrated in vivo widespread opsin expression over the cortical area (7.4±1.0mm in the AP direction, 4.4±1.1mm in the ML direction, N=13 rats) using CED. The optogenetic transduction was also functionally robust, in which both optical modulation of neuronal activity and elicitation of overt motor responses was reliably observed. Comparison with existing method(s)CED led to about 24-fold increase in the volume of opsin expression, compared with the conventional DBD method. The total injection time was also reduced by at least 10 times, if similar extent of expression were to be achieved with the conventional DBD method. ConclusionsCED is a reliable and effective method of virus delivery for optogenetic transduction of planar superficial structures, such as the cortex in rats.

Different patterns of motor activity induce differential plastic changes in pyramidal neurons in the motor cortex of rats: A Golgi study.

Rehabilitation is a process which favors recovery after brain damage involving motor systems, and neural plasticity is the only real resource the brain has for inducing neurobiological events in order to bring about re-adaptation. Rats were placed on a treadmill and made to walk, in different groups, at different velocities and with varying degrees of inclination. Plastic changes in the spines of the apical and basal dendrites of fifth-layer pyramidal neurons in the motor cortices of the rats were detected after study with the Golgi method. Numbers of dendritic spines increased in the three experimental groups, and thin, mushroom, stubby, wide, and branched spines increased or decreased in proportion depending on the motor demands made of each group. Along with the numerical increase of spines, the present findings provide evidence that dendritic spines' geometrical plasticity is involved in the differential performance of motor activity.

The effect of electroacupuncture on proteomic changes in the motor cortex of 6-OHDA Parkinsonian rats

Electroacupuncture (EA) has been reported to alleviate motor deficits in Parkinson’s disease (PD) patients, and PD animal models. However, the mechanisms by which EA improves motor function have not been investigated. We have employed a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate whether EA alters protein expression in the motor cortex. We found that 4weeks of EA treatment significantly improved spontaneous floor plane locomotion and rotarod performance. High-throughput proteomic analysis in the motor cortex was employed. The expression of 54 proteins were altered in the unlesioned motor cortex, and 102 protein expressions were altered in the lesioned motor cortex of 6-OHDA rats compared to sham rats. Compared to non-treatment PD control, EA treatment reversed 6 proteins in unlesioned and 19 proteins in lesioned motor cortex. The present study demonstrated that PD induces proteomic changes in the motor cortex, some of which are rescued by EA treatment. These targeted proteins were mainly involved in increasing autophagy, mRNA processing and ATP binding and maintaining the balance of neurotransmitters.

Diverse action of repeated corticosterone treatment on synaptic transmission, neuronal plasticity, and morphology in superficial and deep layers of the rat motor cortex

One of the adverse effects of prolonged stress in rats is impaired performance of skilled reaching and walking tasks. The mechanisms that lead to these abnormalities are incompletely understood. Therefore, we compared the effects of twice daily repeated corticosterone injections for 7 days on miniature excitatory postsynaptic currents (mEPSCs), as well as on synaptic plasticity and morphology of layers II/III and V pyramidal neurons of the primary motor cortex (M1) of male Wistar rats. Corticosterone treatment resulted in increased frequency, but not amplitude, of mEPSCs in layer II/III neurons accompanied by increased complexity of the apical part of their dendritic tree, with no changes in the density of dendritic spines. The frequency and amplitude of mEPSCs as well as the parameters characterizing the complexity of the dendritic tree were not changed in layer V cells; however, their dendritic spine density was increased. While corticosterone treatment resulted in an increase in the amplitude of field potentials evoked in intralaminar connections within layer II/III, it did not influence field responses in layer V intralaminar connections, as well as the extent of chemically induced layer V long-term potentiation (chemLTP) by the application of tetraethylammonium (TEA, 25 mM). However, chemLTP induction in layer II/III was impaired in slices prepared from corticosterone-treated animals. These data indicate that repeated 7-day administration of exogenous corticosterone induces structural and functional plasticity in the M1, which occurs mainly in layer II/III pyramidal neurons. These findings shed light on potential sites of action and mechanisms underlying stress-induced impairment of motor functions.

Sex differences in somatic and sensory motor development after neonatal anoxia in Wistar rats

Currently, one of the important causes of brain injury in new-borns is the neonatal anoxia which impacts the perinatology services worldwide. Animal models of anoxia have been used to assess its effects at cellular and behavioural levels in all ages, but few studies focus on sex differences. This study aimed to investigate some physical parameters of development, sensorimotor alterations, early neurological reflexes as well as the density of cells in motor and sensorimotor cerebral cortex of adolescent rats submitted to neonatal anoxia. The results presented significant differences in most of the evaluated parameters, such as body weight and lenght, medio-lateral head axis, eruption of superior incisor, palmar grasp, auditory startle, negative geotaxis, showing that neonatal anoxia affects physical parameters and neurological development, with sex differences. Cellular analysis revealed decreased amount of neurons in motor cortex and primary sensory hind limb and forelimb regions in anoxic group, along with gender difference, as compared to control groups. There is an important rationale for performing early assessment of sensorimotor deficits as there is similarity of the model with high risk human neonates and the sequelae in later life periods, which can be inferred from the present results with suggestion of a possible correlation between sensorimotor development delay and cellular changes in sensorimotor cortex. Furthermore, these observed sex dependent alterations certainly will address further studies and should be considered especially in treatments and strategies to avoid or minimize the neonatal anoxic effects.

The (α4)3(β2)2 Stoichiometry of the Nicotinic Acetylcholine Receptor Predominates in the Rat Motor Cortex.

The α4β2 nicotinic acetylcholine receptor (nAChR) is important in central nervous system physiology and in mediating several of the pharmacological effects of nicotine on cognition, attention, and affective states. It is also the likely receptor that mediates nicotine addiction. This receptor assembles in two distinct stoichiometries: (α4)2(β2)3 and (α4)3(β2)2, which are referred to as high-sensitivity (HS) and low-sensitivity (LS) nAChRs, respectively, based on a difference in the potency of acetylcholine to activate them. The physiologic and pharmacological differences between these two receptor subtypes have been described in heterologous expression systems. However, the presence of each stoichiometry in native tissue currently remains unknown. In this study, different ratios of rat α4 and β2 subunit cDNA were transfected into human embryonic kidney 293 cells to create a novel model system of HS and LS α4β2 nAChRs expressed in a mammalian cell line. The HS and LS nAChRs were characterized through pharmacological and biochemical methods. Isolation of surface proteins revealed higher amounts of α4 or β2 subunits in the LS or HS nAChR populations, respectively. In addition, sazetidine-A displayed different efficacies in activating these two receptor stoichiometries. Using this model system, a neurophysiological "two-concentration" acetylcholine or carbachol paradigm was developed and validated to determine α4/β2 subunit stoichiometry. This paradigm was then used in layers I-IV of slices of the rat motor cortex to determine the percent contribution of HS and LS α4β2 receptors in this brain region. We report that the majority of α4β2 nAChRs in this brain region possess a stoichiometry of the (α4)3(β2)2 LS subtype.

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

The pattern of thalamocortical and brain stem projections to the vibrissae-related sensory and motor cortices in de-whiskered congenital hypothyroid rats.

The present study is designed to investigate the plastic organization of the thalamo-cortical (TC) and brain stem afferents of whisker primary sensory (wS1) and motor (wM1) cortical areas in congenital hypothyroid (CH) pups following whisker deprivation (WD) from neonatal to adolescence period. Maternal hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water from early embryonic day 16 to postnatal day (PND) 60. Pregnant rats were divided into intact and CH groups (n=8). In each group, the total whiskers of pups (4 of 8) were trimmed continuously from PND 1 to PND 60. Retrograde tracing technique with WGA-HRP was performed in the present study. Retrogradely labeled neurons were observed in the specific thalamic nuclei (VPM and VL) following separately WGA-HRP injections into wS1/M1 cortical areas. The number of labeled cells in the VPM, VL, VM and PO nuclei of the thalamus significantly decreased in CH offsprings rats (P<0.05). Neonatal WD did not show any significant effects on the number of VPM, VL, VM and PO labeled projection neurons to wS1 and wM1 cortical areas. In addition, retrogradely labeled neurons in dorsal raphe (DR) and locus coeruleus (LC) nuclei were observed in all experimental groups. The number of DR and LC labeled neurons were higher in the CH and whisker deprived groups compared to their matching controls (P<0.05). Upon our results, CH and WD had no synergic or additive effects on the TC and brain stem afferent patterns of barrel sensory and motor cortices.

Localized over expression of FGF9 in the rat motor cortex reproduces the pathological features of grey matter lesions in progressive multiple sclerosis. (P2.364)

Localized over expression of FGF9 in the rat motor cortex reproduces the pathological features of grey matter lesions in progressive multiple sclerosis. (P2.364)

Functional remodeling of subtype-specific markers surrounding implanted neuroprostheses.

Microelectrode arrays implanted in the brain are increasingly used for the research and treatment of intractable neurological disease. However, local neuronal loss and glial encapsulation are known to interfere with effective integration and communication between implanted devices and brain tissue, where these observations are typically based on assessments of broad neuronal and astroglial markers. However, both neurons and astrocytes comprise heterogeneous cellular populations that can be further divided into subclasses based on unique functional and morphological characteristics. In this study, we investigated whether or not device insertion causes alterations in specific subtypes of these cells. We assessed the expression of both excitatory and inhibitory markers of neurotransmission (vesicular glutamate and GABA transporters, VGLUT1 and VGAT, respectively) surrounding single-shank Michigan-style microelectrode arrays implanted in the motor cortex of adult rats by use of quantitative immunohistochemistry. We found a pronounced shift from significantly elevated VGLUT1 within the initial days following implantation to relatively heightened VGAT by the end of the 4-wk observation period. Unexpectedly, we observed VGAT positivity in a subset of reactive astrocytes during the first week of implantation, indicating heterogeneity in early-responding encapsulating glial cells. We coupled our VGLUT1 data with the evaluation of a second marker of excitatory neurons (CamKiiα); the results closely paralleled each other and underscored a progression from initially heightened to subsequently weakened excitatory tone in the neural tissue proximal to the implanted electrode interface (within 40 μm). Our results provide new evidence for subtype-specific remodeling surrounding brain implants that inform observations of suboptimal integration and performance.NEW & NOTEWORTHY We report novel changes in the local expression of excitatory and inhibitory synaptic markers surrounding microelectrode arrays implanted in the motor cortex of rats, where a progressive shift toward increased inhibitory tone was observed over the 4-wk observation period. The result was driven by declining glutamate transporter expression (VGLUT1) in parallel with increasing GABA transporter expression (VGAT) over time, where a reactive VGAT+ astroglial subtype made an unexpected contribution to our findings.

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration “thin” spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin‐positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32‐postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons.

P152 After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats

Purpose Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. Methods These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. A Teflon-coated stainless-steel twisted-wire electrode (125 μm exposed tips; 0.5 mm tip separation) was placed in the left corpus callosum (3.0 mm anterior to bregma, 2.0 mm lateral to midline, 3.0 mm below the dural surface). The electrode position was adjusted in depth to maximize evoked field potentials at the surface of the skull (Fig. 1) Download : Download high-res image (401KB) Download : Download full-size image . Reference and ground electrodes were attached to the exposed scalp tissue and to a stereotaxic screw. To evoke field potentials in the right motor cortex, biphasic, square-wave constant current stimulation pulses with a duration of 0.1 ms and an intensity of 300 μA were delivered to the left corpus callosum at 30 s intervals using a A365 stimulus isolator. Anodal tDCS current was applied at an intensity of 250 μA for 20 min (n = 8) or 500 μA for 10 min (n = 3) using a direct current stimulator. These intensities for tDCS were based on previously reported limits (52,400 C/m2) for safe stimulation. Results Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS (Fig. 2) Download : Download high-res image (269KB) Download : Download full-size image . To induce these long-lasting effects, a sufficient duration of stimulation (20 min or more) was found to may be required rather than high stimulation intensity. Conclusion We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity. This research was supported by National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014R1A2A2A01002501).