Increase In Spike Activity Research Articles

Understanding novel neuromodulation pathways in tDCS: brain stem recordings in rats during trigeminal nerve direct current stimulation

tDCS is widely assumed to cause neuromodulation via the electric field in the cortex acting directly on cortical neurons. However, recent evidence suggests that tDCS may indirectly influence brain activity through cranial nerve pathways, notably the trigeminal nerve, but these neuromodulatory pathways remain unexplored. To investigate the first stages in this potential pathway we developed an animal model to study the effect of trigeminal nerve direct current stimulation (TN-DCS) on neuronal activity in the principal sensory nucleus (NVsnpr) and the mesencephalic nucleus of the trigeminal nerve (MeV). We conducted experiments on twenty-four male Sprague Dawley rats (n = 10 NVsnpr, n = 10 MeV during anodic stimulation, and n = 4 MeV during cathodic stimulation). DC stimulation, ranging from 0.5 to 3 mA, targeted the trigeminal nerve’s marginal branch. Concurrently, single-unit electrophysiological recordings were obtained using a 32-channel silicon probe, encompassing three 1-min intervals: pre, during, and post-stimulation. Xylocaine trigeminal nerve blockage served as a control. TN-DCS increased neuronal spiking activity in both NVsnpr and MeV, returning to baseline during the post-stimulation phase. The 3 mA DC stimulation of the blocked trigeminal nerve failed to induce increased spiking activity in the trigeminal nuclei. These findings provide empirical support for trigeminal nuclei modulation via TN-DCS, suggesting the cranial nerve pathways could play a role in mediating the tDCS effects in humans.

Effects of kappa-opioid agonist U-50488 and p38 MAPK inhibitor SB203580 on the spike activity of pyramidal neurons in the basolateral amygdala

Introduction: Kappa-opioid receptor (KOR) signaling in the basolateral amygdala (BLA) underlies KOR agonist-induced aversion. In this study, we aimed to understand the individual and combined effects of KOR agonist U-50488 and p38 MAPK inhibitor SB203580 on the spiking activity of pyramidal neurons in the BLA to shed light on the complex interplay between KORs, the p38 MAPK, and neuronal excitability. Materials and Methods: Electrophysiological experiments were performed using the patch-clamp technique in the whole-cell configuration. Rat brain slices containing the amygdala were prepared, and pyramidal neurons within the BLA were visually patched and recorded in the current clamp mode. The neurons were identified by their accommodation properties and neural activity signals were amplified and analyzed. Using local perfusion, we obtained three dose-response curves for: (a) U-50488 (0.001–10 μM); (b) U-50488 (0.001–10 μM) in the presence of SB203580 (1 μM); and (c) U-50488 (0.01–10 μM) in the presence of SB203580 (5 μM). Results: After the application of U-50488, pyramidal neurons had a higher action potential firing rate in response to a current injection than control neurons (p<0.001). The dose-dependent curves we obtained indicate that the combination of U-50488 and SB203580 results in non-competitive antagonism. This conclusion is supported by the observed change in the curve’s slope with reduction in the maximum effect of U-50488. Thus, it can be assumed that the increase in spike activity of pyramidal neurons of the amygdala is mediated through the beta-arrestin pathway. When this pathway is blocked, the spike activity reverts to its baseline level. Conclusion: Our study found that the KOR agonist-induced spiking activity of the BLA pyramidal neurons is mediated by the beta-arrestin pathway and can be suppressed by the application of the p38 MAPK inhibitor SB203580.

Laminar specificity of the auditory perceptual awareness negativity: A biophysical modeling study.

How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-5 (L5) pyramidal neurons. In turn, this leads to increased local field potential activity, increased spiking activity in L5 pyramidal neurons, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity.

Modulation of cerebellar cortical, cerebellar nuclear and vestibular nuclear activity using alternating electric currents.

Cerebellar transcranial alternating current stimulation (ctACS) has shown promise as a therapeutic modality for treating a variety of neurological disorders, and for affecting normal learning processes. Yet, little is known about how electric fields induced by applied currents affect cerebellar activity in the mammalian cerebellum under in vivo conditions. Alternating current (AC) stimulation with frequencies from 0.5 to 20 Hz was applied to the surface of the cerebellum in anesthetized rats. Extracellular recordings were obtained from Purkinje cells (PC), cerebellar and vestibular nuclear neurons, and other cerebellar cortical neurons. AC stimulation modulated the activity of all classes of neurons. Cerebellar and vestibular nuclear neurons most often showed increased spike activity during the negative phase of the AC stimulation. Purkinje cell simple spike activity was also increased during the negative phase at most locations, except for the cortex directly below the stimulus electrode, where activity was most often increased during the positive phase of the AC cycle. Other cortical neurons showed a more mixed, generally weaker pattern of modulation. The patterns of Purkinje cell responses suggest that AC stimulation induces a complex electrical field with changes in amplitude and orientation between local regions that may reflect the folding of the cerebellar cortex. Direct measurements of the induced electric field show that it deviates significantly from the theoretically predicted radial field for an isotropic, homogeneous medium, in both its orientation and magnitude. These results have relevance for models of the electric field induced in the cerebellum by AC stimulation.

Methcathinone Increases Visually-evoked Neuronal Activity and Enhances Sensory Processing Efficiency in Mice.

Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca2+ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.

Regional healthy brain activity, glioma occurrence and symptomatology.

It is unclear why exactly gliomas show preferential occurrence in certain brain areas. Increased spiking activity around gliomas leads to faster tumour growth in animal models, while higher non-invasively measured brain activity is related to shorter survival in patients. However, it is unknown how regional intrinsic brain activity, as measured in healthy controls, relates to glioma occurrence. We first investigated whether gliomas occur more frequently in regions with intrinsically higher brain activity. Second, we explored whether intrinsic cortical activity at individual patients’ tumour locations relates to tumour and patient characteristics.Across three cross-sectional cohorts, 413 patients were included. Individual tumour masks were created. Intrinsic regional brain activity was assessed through resting-state magnetoencephalography acquired in healthy controls and source-localized to 210 cortical brain regions. Brain activity was operationalized as: (i) broadband power; and (ii) offset of the aperiodic component of the power spectrum, which both reflect neuronal spiking of the underlying neuronal population. We additionally assessed (iii) the slope of the aperiodic component of the power spectrum, which is thought to reflect the neuronal excitation/inhibition ratio. First, correlation coefficients were calculated between group-level regional glioma occurrence, as obtained by concatenating tumour masks across patients, and group-averaged regional intrinsic brain activity. Second, intrinsic brain activity at specific tumour locations was calculated by overlaying patients’ individual tumour masks with regional intrinsic brain activity of the controls and was associated with tumour and patient characteristics.As proposed, glioma preferentially occurred in brain regions characterized by higher intrinsic brain activity in controls as reflected by higher offset. Second, intrinsic brain activity at patients’ individual tumour locations differed according to glioma subtype and performance status: the most malignant isocitrate dehydrogenase-wild-type glioblastoma patients had the lowest excitation/inhibition ratio at their individual tumour locations as compared to isocitrate dehydrogenase-mutant, 1p/19q-codeleted glioma patients, while a lower excitation/inhibition ratio related to poorer Karnofsky Performance Status, particularly in codeleted glioma patients.In conclusion, gliomas more frequently occur in cortical brain regions with intrinsically higher activity levels, suggesting that more active regions are more vulnerable to glioma development. Moreover, indices of healthy, intrinsic excitation/inhibition ratio at patients’ individual tumour locations may capture both tumour biology and patients’ performance status. These findings contribute to our understanding of the complex and bidirectional relationship between normal brain functioning and glioma growth, which is at the core of the relatively new field of ‘cancer neuroscience’.

The impact of closed-loop intracortical stimulation on neural activity in brain-injured, anesthetized animals

BackgroundAcquired brain injuries, such as stroke, are a major cause of long-term disability worldwide. Intracortical microstimulation (ICMS) can be used successfully to assist in guiding appropriate connections to restore lost sensorimotor integration. Activity-Dependent Stimulation (ADS) is a specific type of closed-loop ICMS that aims at coupling the activity of two different brain regions by stimulating one in response to activity in the other. Recently, ADS was used to effectively promote behavioral recovery in rodent models following a unilateral traumatic brain injury in the primary motor cortex. While behavioral benefits have been described, the neurophysiological changes in spared areas in response to this type of stimulation have not been fully characterized. Here we explored how single-unit spiking activity is impacted by a focal ischemic lesion and, subsequently, by an ADS treatment.MethodsIntracortical microelectrode arrays were implanted in the ipsilesional rostral forelimb area (RFA) to record spike activity and to trigger intracortical microstimulation in the primary somatosensory area (S1) of anaesthetized Long Evans rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. Activity from both RFA and S1 was recorded and analyzed off-line by evaluating possible changes, either induced by the lesion in the Control group or by stimulation in the ADS group.ResultsWe found that the ischemic lesion in the motor area led to an overall increase in spike activity within RFA and a decrease in S1 with respect to the baseline condition. Subsequent treatment with ADS increased the firing rate in both RFA and S1. Post-stimulation spiking activity was significantly higher compared to pre-stimulation activity in the ADS animals versus non-stimulated controls. Moreover, stimulation promoted the generation of highly synchronized bursting patterns in both RFA and S1 only in the ADS group.ConclusionsThis study describes the impact on single-unit activity in ipsilesional areas immediately following a cortical infarct and demonstrates that application of ADS is effective in altering this activity.

Changes of interictal epileptiform discharges during medication withdrawal and seizures: A scalp EEG marker of epileptogenicity

ObjectiveTo determine the influence of antiseizure medication (ASM) withdrawal on interictal epileptogenic discharges (IEDs) in scalp-EEG and seizure propensity. MethodsWe included 35 adult unifocal epilepsy patients admitted for presurgical evaluation in the EEG and Epilepsy Unit of Geneva between 2016 and 2020, monitored for at least 5 days. ASM was individually tapered down, and automated IED detection was performed using Epilog PreOp (Epilog NV, Belgium, Ghent). We compared spike rate per hour (SR) at day 1 when patients were on full medication (baseline) with SR at the day with the lowest dose of medication. To determine possible peri-ictal changes of SR, we compared SR 8 h before and after a seizure with the SR at the same time of the baseline day. ResultsOur results showed a significant increase in spiking activity in the day of lowest drug load if compared to spike rate at day on full medication (p < 0.001). The total amount of spikes during 24 h correlated significantly with seizure occurrence (p < 0.0001). We also revealed significant increase in peri-ictal SR, in particular 2–4 h preceding a seizure (p = 0.05) extending up to 3 h after the seizure (p = 0.03) with a short decrease just before seizure occurrence. ConclusionsOur results suggest that SR increases with medication withdrawal and particularly before and after seizures. There is a complex pattern of increase and decrease around seizure onset which explains divergent results in previous studies. SignificancePrecise spike counting at similar circadian periods for a patient could help to determine the risk of seizure occurrence in a personalized fashion.

Audiotactile interactions in the mouse cochlear nucleus

Multisensory integration of auditory and tactile information occurs already at the level of the cochlear nucleus. Rodents use their whiskers for tactile perception to guide them in their exploration of the world. As nocturnal animals with relatively poor vision, audiotactile interactions are of great importance for this species. Here, the influence of whisker deflections on sound-evoked spiking in the cochlear nucleus was investigated in vivo in anesthetized mice. Multichannel, silicon-probe electrophysiological recordings were obtained from both the dorsal and ventral cochlear nucleus. Whisker deflections evoked an increased spiking activity in fusiform cells of the dorsal cochlear nucleus and t-stellate cells in ventral cochlear nucleus, whereas bushy cells in the ventral cochlear nucleus showed a more variable response. The response to broadband noise stimulation increased in fusiform cells and primary-like bushy cells when the sound stimulation was preceded (~ 20 ms) by whisker stimulation. Multi-sensory integration of auditory and whisker input can thus occur already in this early brainstem nucleus, emphasizing the importance of early integration of auditory and somatosensory information.

Effects of direct current stimulation on synaptic plasticity in a single neuron

BackgroundTranscranial direct current stimulation (DCS) has lasting effects that may be explained by a boost in synaptic long-term potentiation (LTP). We hypothesized that this boost is the result of a modulation of somatic spiking in the postsynaptic neuron, as opposed to indirect network effects. To test this directly we record somatic spiking in a postsynaptic neuron during LTP induction with concurrent DCS. MethodsWe performed rodent in-vitro patch-clamp recordings at the soma of individual CA1 pyramidal neurons. LTP was induced with theta-burst stimulation (TBS) applied concurrently with DCS. To test the causal role of somatic polarization, we manipulated polarization via current injections. We also used a computational multi-compartment neuron model that captures the effect of electric fields on membrane polarization and activity-dependent synaptic plasticity. ResultsTBS-induced LTP was enhanced when paired with anodal DCS as well as depolarizing current injections. In both cases, somatic spiking during the TBS was increased, suggesting that evoked somatic activity is the primary factor affecting LTP modulation. However, the boost of LTP with DCS was less than expected given the increase in spiking activity alone. In some cells, we also observed DCS-induced spiking, suggesting DCS also modulates LTP via induced network activity. The computational model reproduces these results and suggests that they are driven by both direct changes in postsynaptic spiking and indirect changes due to network activity. ConclusionDCS enhances synaptic plasticity by increasing postsynaptic somatic spiking, but we also find that an increase in network activity may boost but also limit this enhancement.

AAV vectors to study the functional consequences of neuronal and astrocytic tau pathology using in vivo 2‐photon imaging

AbstractBackgroundTau pathology is a defining histopathological feature of Alzheimer’s disease (AD) and primary tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Whereas AD is mostly characterized by neuronal tau pathology, primary tauopathies such as PSP and CBD also present with glial tau pathology. How tau pathology affects the activity of distinct neuronal cell types (e.g. interneurons) or glial cells (e.g. astrocytes) is currently unknown. We have developed adeno‐associated virus (AAV)‐based tauopathy models of neuronal and astrocytic tau pathology to study the functional consequences of tau pathology using in vivo 2‐photon imaging.MethodWe present AAV vectors expressing human truncated tau (amino acids 151‐391/4R) and red fluorophore mCherry in equal ratio under the neuronal human synapsin promotor (AAV‐hSyn‐htTau) or the astrocytic GFAP promotor (AAV‐GFAP‐htTau). AAVs expressing only mCherry under the same promotors were used as controls. AAVs were injected into the hippocampus of wild‐type mice for histological, biochemical, and behavioral characterization.AAV‐hSyn‐htTau was injected intracerebroventricularly in PV‐Cre mice to study the effects of tau pathology on pyramidal neurons or interneurons using in vivo 2‐photon calcium imaging. AAV‐GFAP‐htTau was injected into the cortex of wild‐type or CX3CR1‐YFP mice to study the effects of astrocytic tau pathology on neuronal activity or microglia using in vivo imaging, respectively.ResultAAV‐hSyn‐htTau and AAV‐GFAP‐htTau both induced widespread expression of mCherry and hyperphosphorylated tau in neurons or astrocytes, respectively. Only the neuronal model induced abundant sarkosyl insoluble tau and methoxy‐XO4+ aggregated tau. In vivo 2‐photon calcium imaging of cortical neurons revealed increased spiking activity in truncated tau‐expressing PV+ interneurons, but not in pyramidal cells, suggesting that tau‐mediated alteration of interneuron activity is an early pathological event. No cognitive impairments were detected at early timepoints.Astrocytic tau pathology led to inflammatory changes of blood vessels, such as upregulation of adhesion molecules VCAM1 and ICAM1. No changes in cognition or neuronal spiking activity were detected at the examined timepoints. Analysis of microglial morphology and motility is currently ongoing.ConclusionAAV‐based tauopathy models are attractive tools to study the consequences of neuronal and glial tau pathology in vivo. Funding: VEGA 2/0135/18 and SyDAD (Horizon 2020, 676144)

Investigating the Effects of Mechanical Stimulation on Retinal Ganglion Cell Spontaneous Spiking Activity.

Mechanical forces are increasingly recognized as major regulators of several physiological processes at both the molecular and cellular level; therefore, a deep understanding of the sensing of these forces and their conversion into electrical signals are essential for studying the mechanosensitive properties of soft biological tissues. To contribute to this field, we present a dual-purpose device able to mechanically stimulate retinal tissue and to record the spiking activity of retinal ganglion cells (RGCs). This new instrument relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with high-density multi-electrode array (HD-MEAs) to simultaneously record the spontaneous activity of the retina. In this paper, we introduce this instrument, describe its technical characteristics, and present a proof-of-concept experiment that shows how RGC spiking activity of explanted mice retinas respond to mechanical micro-stimulations of their photoreceptor layer. The data suggest that, under specific conditions of indentation, the retina perceive the mechanical stimulation as modulation of the visual input, besides the longer time-scale of activation, and the increase in spiking activity is not only localized under the indentation probe, but it propagates across the retinal tissue.

The spiking and secretory activity of oxytocin neurones in response to osmotic stimulation: a computational model.

A quantitative model of oxytocin neurones that combines a spiking model, a model of stimulus-secretion coupling and a model of plasma clearance of oxytocin was tested. To test the model, a variety of sources of published data were used that relate either the electrical activity of oxytocin cells or the secretion of oxytocin to experimentally induced changes in plasma osmotic pressure. To use these data to test the model, the experimental challenges involved were computationally simulated. The model predictions closely matched the reported outcomes of the different experiments. Magnocellular vasopressin and oxytocin neurones in the rat hypothalamus project to the posterior pituitary, where they secrete their products into the bloodstream. In rodents, both vasopressin and oxytocin magnocellular neurones are osmoresponsive, and their increased spiking activity is mainly a consequence of an increased synaptic input from osmoresponsive neurons in regions adjacent to the anterior wall of the third ventricle. Osmotically stimulated vasopressin secretion promotes antidiuresis while oxytocin secretion promotes natriuresis. In this work we tested a previously published computational model of the spiking and secretion activity of oxytocin cells against published evidence of changes in spiking activity and plasma oxytocin concentration in response to different osmotic challenges. We show that integrating this oxytocin model with a simple model of the osmoresponsive inputs to oxytocin cells achieves a strikingly close match to diverse sources of data. Comparing model predictions with published data using bicuculline to block inhibitory GABA inputs supports the conclusion that inhibitory inputs and excitatory inputs are co-activated by osmotic stimuli. Finally, we studied how the gain of osmotically stimulated oxytocin release changes in the presence of a hypovolaemic stimulus, showing that this is best explained by an inhibition of an osmotically regulated inhibitory drive to the magnocellular neurones.

347-LB: MEA Technology as an Easy Electrophysiological Approach for Noninvasive Recordings of Intact Murine and Human Islets

Increase of blood glucose concentration leads to glucose-induced electrical activity of pancreatic beta-cells followed by insulin secretion. Electrical activity appears in glucose concentration-dependent oscillations easily recorded by microelectrode arrays (MEA). In comparison to other electrophysiological techniques MEAs can record non-invasively from intact islets and can be used for long term studies to investigate chronic effects of drugs. Murine islets or islets isolated from human biopsies were used for recordings. Electrical activity was quantified as fraction of plateau Phase (FOPP) or number of single spike activity. Islets were placed via suction or cultivated on MEAs. The glucose concentration response curve recorded with murine islets plotted as FOPP revealed a half-maximal activity of 12 ± 2 mM which is in line with traditional methods like e.g., with intracellular electrodes. Glucose-induced activity of cultured islets remains stable over a month. Application of well-known substances (like e.g., diazoxide, tolbutamide) matched regular results. Human islets displayed typical glucose-induced activity (10 mM). Validation studies showed the existence of functional KATP channels and TTX reduced spike activity from 1047 ± 314 to 199 ± 90 spikes/5min after the application of 300 nM TTX. The washout led to an increased spike activity of 779 ± 301 spikes/minutes. The glucose concentration response curve revealed an EC50 value of 8 ± 3 mM glucose. The glucose responsiveness recorded with the MEA Technology is in line with other reports showing that the EC50 value of human beta-cells (∼ 6 mM) is lower than in mouse beta-cells. MEA Technology allows medium throughput recordings from up to 40 intact islets simultaneously. While previous electrophysiological attempts failed MEAs offer large scale research in both academics and industry. The principle of function is not limited to rodent but is also applicable to human or stem cell derived islets of Langerhans. Disclosure S. Schönecker: None. M. Oza: Employee; Self; Multichannel Systems, Gmbh. U. Kraushaar: None.

Neural Representation of Motor Output, Context and Behavioral Adaptation in Rat Medial Prefrontal Cortex During Learned Behavior.

Selecting behavioral outputs in a dynamic environment is the outcome of integrating multiple information streams and weighing possible action outcomes with their value. Integration depends on the medial prefrontal cortex (mPFC), but how mPFC neurons encode information necessary for appropriate behavioral adaptation is poorly understood. To identify spiking patterns of mPFC during learned behavior, we extracellularly recorded neuronal action potential firing in the mPFC of rats performing a whisker-based “Go”/“No-go” object localization task. First, we identify three functional groups of neurons, which show different degrees of spiking modulation during task performance. One group increased spiking activity during correct “Go” behavior (positively modulated), the second group decreased spiking (negatively modulated) and one group did not change spiking. Second, the relative change in spiking was context-dependent and largest when motor output had contextual value. Third, the negatively modulated population spiked more when rats updated behavior following an error compared to trials without integration of error information. Finally, insufficient spiking in the positively modulated population predicted erroneous behavior under dynamic “No-go” conditions. Thus, mPFC neuronal populations with opposite spike modulation characteristics differentially encode context and behavioral updating and enable flexible integration of error corrections in future actions.

Neurotropism and behavioral changes associated with Zika infection in the vector Aedes aegypti

Understanding Zika virus infection dynamics is essential, as its recent emergence revealed possible devastating neuropathologies in humans, thus causing a major threat to public health worldwide. Recent research allowed breakthrough in our understanding of the virus and host pathogenesis; however, little is known on its impact on its main vector, Aedes aegypti. Here we show how Zika virus targets Aedes aegypti’s neurons and induces changes in its behavior. Results are compared to dengue virus, another flavivirus, which triggers a different pattern of behavioral changes. We used microelectrode array technology to record electrical spiking activity of mosquito primary neurons post infections and discovered that only Zika virus causes an increase in spiking activity of the neuronal network. Confocal microscopy also revealed an increase in synapse connections for Zika virus-infected neuronal networks. Interestingly, the results also showed that mosquito responds to infection by overexpressing glutamate regulatory genes while maintaining virus levels. This neuro-excitation, possibly via glutamate, could contribute to the observed behavioral changes in Zika virus-infected Aedes aegypti females. This study reveals the importance of virus-vector interaction in arbovirus neurotropism, in humans and vector. However, it appears that the consequences differ in the two hosts, with neuropathology in human host, while behavioral changes in the mosquito vector that may be advantageous to the virus.

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells.

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation.

Cerebrospinal fluid from Dementia with Lewy body patients suppresses neuronal network activity

Cerebrospinal fluid from Dementia with Lewy body patients suppresses neuronal network activity

Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial temporal lobe epilepsy

Patients with medically refractory epilepsy may benefit from resective epilepsy surgery. However even the best centers experience surgical failures. It is therefore important to find techniques that may aid in neurosurgical planning of epileptic focus resection. Recordings of electrical brain activity with EEG during seizures reveal abnormal cortical hypersynchronization. Between seizures the EEG often shows interictal depolarizing phenomena such as spikes reflecting an irritable focus of the brain.In the present study we investigated the effect of intravenous remifentanil on the spike activity in the temporal neocortex and hippocampus. We examined 65 patients with mesial temporal lobe epilepsy during surgery, prior to resection. We used a 20-lead grid on the cortex and a 4-lead strip in the lateral ventricle on the hippocampus. At least two 3-min periods of ECoG were recorded – before and after remifentanil injection. In a number of patients we examined the effect of repeated injections in order to estimate the dose-response curve.We describe a significant effect of remifentanil on the average spike activity with an increment from 16 spikes per minute at baseline to 36 spikes per minute after remifentanil injection (p<0.0001). The increase in spike activity was typically seen after 40–50s. When mu-receptors were antagonized with a preceding injection of naloxone, spike activity increased 25% in response to remifentanil as opposed to 80% when remifentanil was preceded by placebo. In only seven out of 59 patients did the injection of remifentanil change the topographic location of the spike focus. Typically administration of remifentanil led to a focus of increased spike count. Activity in other areas was suppressed making the focus stand out from the background.Our observation that remifentanil potentiates spike activity is in agreement with previous findings from smaller studies. Furthermore, we were able to describe the pharmacodynamics of the remifentanil effect on spike activity. Peri-operative provocation with remifentanil may play a future role in guiding neurosurgical intervention during epilepsy resection surgery.

Audiovisual Distraction Increases Prefrontal Cortical Neuronal Activity and Impairs Attentional Performance in the Rat.

Involvement of attentional processes is generally evidenced by disruption of behavior in the presence of distracting stimuli. The medial prefrontal cortex (mPFC) seems to play a role in fine-tuning activity during attentional tasks. A novel titration variant of the 5-choice serial reaction time task (5-choice serial reaction time titration variant [5CTV]) that adjusts task difficulty based on subject performance was used to evaluate the effects of audiovisual distraction (DSTR) on performance and mPFC single spike activity and local field potential (LFP). Attention was impaired in the 5CTV from DSTR, and mPFC spike activity was increased, whereas LFP was reduced. The increased spike activity in the mPFC in conjunction with DSTR suggests that conflicting attentional demands may contribute to the reduced task performance. As both hypo- and hyperactivation of the mPFC may contribute to attentional disruption, further studies using the 5CTV are needed to understand mPFC activity changes in real time during disruption of performance by other types of behavioral or neurobiological manipulations.