Local Field Potential Recordings Research Articles

In vivo electrophysiological study of the targeting of 5-HT3 receptor-expressing cortical interneurons by the multimodal antidepressant, vortioxetine.

The antidepressant vortioxetine has high affinity for the ionotropic 5‐HT3 receptor (5‐HT3R) as well as other targets including the 5‐HT transporter. The procognitive effects of vortioxetine have been linked to altered excitatory:inhibitory balance in cortex. Thus, vortioxetine purportedly inhibits cortical 5‐HT3R‐expressing interneurons (5‐HT3R‐INs) to disinhibit excitatory pyramidal neurons. The current study determined for the first time the effect of vortioxetine on the in vivo firing of putative 5‐HT3R‐INs whilst simultaneously recording pyramidal neuron activity using cortical slow‐wave oscillations as a readout. Extracellular single unit and local field potential recordings were made in superficial layers of the prefrontal cortex of urethane‐anaesthetised rats. 5‐HT3R‐INs were identified by a short‐latency excitation evoked by electrical stimulation of the dorsal raphe nucleus (DRN). Juxtacellular‐labelling found such neurons had the morphological and immunohistochemical properties of 5‐HT3R‐INs: basket cell or bipolar cell morphology, expression of 5‐HT3R‐IN markers and parvalbumin‐immunonegative. Vortioxetine inhibited the short‐latency DRN‐evoked excitation of 5‐HT3R‐INs and simultaneously decreased cortical slow wave oscillations, indicative of pyramidal neuron activation. Likewise, the 5‐HT3R antagonist ondansetron inhibited the short‐latency DRN‐evoked excitation of 5‐HT3R‐INs. However unlike vortioxetine, ondansetron did not decrease cortical slow‐wave oscillations, suggesting a dissociation between this effect and inhibition of 5‐HT3R‐INs. The 5‐HT reuptake inhibitor escitalopram had no consistent effect on any electrophysiological parameter measured. Overall, the current findings suggest that vortioxetine simultaneously inhibits (DRN‐evoked) 5‐HT3R‐INs and excites pyramidal neurons, thereby changing the excitatory:inhibitory balance in cortex. However, under the current experimental conditions, these two effects were dissociable with only the former likely involving a 5‐HT3R‐mediated mechanism.

The Listening Zone of Human Electrocorticographic Field Potential Recordings.

Intracranial electroencephalographic (icEEG) recordings provide invaluable insights into neural dynamics in humans because of their unmatched spatiotemporal resolution. Yet, such recordings reflect the combined activity of multiple underlying generators, confounding the ability to resolve spatially distinct neural sources. To empirically quantify the listening zone of icEEG recordings, we computed correlations between signals as a function of distance (full width at half maximum; FWHM) between 8752 recording sites in 71 patients (33 female) implanted with either subdural electrodes (SDEs), stereo-encephalography electrodes (sEEG), or high-density sEEG electrodes. As expected, for both SDEs and sEEGs, higher frequency signals exhibited a sharper fall off relative to lower frequency signals. For broadband high γ (BHG) activity, the mean FWHM of SDEs (6.6 ± 2.5 mm) and sEEGs in gray matter (7.14 ± 1.7 mm) was not significantly different; however, FWHM for low frequencies recorded by sEEGs was 2.45 mm smaller than SDEs. White matter sEEGs showed much lower power for frequencies 17–200 Hz (q < 0.01) and a much broader decay (11.3 ± 3.2 mm) than gray matter electrodes (7.14 ± 1.7 mm). The use of a bipolar referencing scheme significantly lowered FWHM for sEEGs, relative to a white matter reference or a common average reference (CAR). These results outline the influence of array design, spectral bands, and referencing schema on local field potential recordings and source localization in icEEG recordings in humans. The metrics we derive have immediate relevance to the analysis and interpretation of both cognitive and epileptic data.

Lateralized and Region-Specific Thalamic Processing of Lexical Status during Reading Aloud.

To explore whether the thalamus participates in lexical status (word vs nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep-brain stimulation lead implantation during a visually cued word and nonword reading-aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multiunit spiking activity, occurring shortly before and predominantly time locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization of thalamic broadband gamma selectivity for lexical status. In addition, this lateralized lexicality effect on broadband gamma activity was strongest in more anterior thalamic locations, regions which are more likely to receive basal ganglia than cerebellar afferents and have extensive connections with prefrontal cortex including Brodmann's areas 44 and 45, regions consistently associated with grapheme-to-phoneme conversions. These results demonstrate active thalamic participation in reading aloud and provide direct evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.SIGNIFICANCE STATEMENT Despite the corticocentric focus of most experimental work and accompanying models, there is increasing recognition of the role of subcortical structures in speech and language. Using local field potential recordings in neurosurgical patients, we demonstrated that the thalamus participates in lexical status (word vs nonword) processing during spoken word production, in a lateralized and region-specific manner. These results provide direct evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.

State-dependent olfactory processing in freely behaving mice.

SUMMARYDecreased responsiveness to sensory stimuli during sleep is presumably mediated via thalamic gating. Without an obligatory thalamic relay in the olfactory system, the anterior piriform cortex (APC) is suggested to be a gate in anesthetized states. However, olfactory processing in natural sleep states remains undetermined. Here, we simultaneously record local field potentials (LFPs) in hierarchical olfactory regions (olfactory bulb [OB], APC, and orbitofrontal cortex) while optogenetically activating olfactory sensory neurons, ensuring consistent peripheral inputs across states in behaving mice. Surprisingly, evoked LFPs in sleep states (both non-rapid eye movement [NREM] and rapid eye movement [REM]) are larger and contain greater gamma-band power and cross-region coherence (compared to wakefulness) throughout the olfactory pathway, suggesting the lack of a central gate. Single-unit recordings from the OB and APC reveal a higher percentage of responsive neurons during sleep with a higher incidence of suppressed firing. Additionally, nasal breathing is slower and shallower during sleep, suggesting a partial peripheral gating mechanism.

Arc-Mediated Plasticity in the Paraventricular Thalamic Nucleus Promotes Habituation to Stress

BackgroundHabituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of posttraumatic stress disorder. In rodents, habituation is observed in neural, neuroendocrine, and behavioral responses to repeated exposure to predictable and moderately intense stress or restraint. We previously demonstrated that lesioning the posterior paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown. MethodsBehavioral and neuroendocrine habituation was assessed in adult male Sprague Dawley rats using the repeated restraint paradigm. Pan-neuronal and Cre-dependent DREADDs (designer receptors exclusively activated by designer drugs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using small interfering RNA. Structural plasticity of pPVT neurons was assessed using Golgi staining. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set shifting task was used to assess mPFC-dependent behavior. ResultsHere, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility. ConclusionsOur results demonstrate that Arc induction in the pPVT regulates habituation and mPFC function. Therapies that improve synaptic plasticity during posttraumatic stress disorder therapy may enhance habituation and the efficacy of posttraumatic stress disorder treatment.

From the North Sea to Drug Repurposing, the Antiseizure Activity of Halimide and Plinabulin.

PharmaSea performed large-scale in vivo screening of marine natural product (MNP) extracts, using zebrafish embryos and larvae, to identify compounds with the potential to treat epilepsy. In this study, we report the discovery of two new antiseizure compounds, the 2,5-diketopiperazine halimide and its semi-synthetic analogue, plinabulin. Interestingly, these are both known microtubule destabilizing agents, and plinabulin could have the potential for drug repurposing, as it is already in clinical trials for the prevention of chemotherapy-induced neutropenia and treatment of non-small cell lung cancer. Both halimide and plinabulin were found to have antiseizure activity in the larval zebrafish pentylenetetrazole (PTZ) seizure model via automated locomotor analysis and non-invasive local field potential recordings. The efficacy of plinabulin was further characterized in animal models of drug-resistant seizures, i.e., the larval zebrafish ethyl ketopentenoate (EKP) seizure model and the mouse 6 Hz psychomotor seizure model. Plinabulin was observed to be highly effective against EKP-induced seizures, on the behavioral and electrophysiological level, and showed activity in the mouse model. These data suggest that plinabulin could be of interest for the treatment of drug-resistant seizures. Finally, the investigation of two functional analogues, colchicine and indibulin, which were observed to be inactive against EKP-induced seizures, suggests that microtubule depolymerization does not underpin plinabulin’s antiseizure action.

HP16: Estimating synaptic transmission changes in the epileptic brain with and without stimulation

Computational modeling is a powerful tool for exploring brain mechanisms underlying neurophysiological observations. Nowadays, it is increasingly used to design and evaluate the effect of therapeutic interventions. In this contribution, the computational approach is used to investigate the effects of single pulse and repetitive electrical stimulation on excitation, slow dendritic and fast somatic inhibition in a rodent model of epilepsy. Method: Building on the modeling work of Wendling et al. (J Clin Neurophysiol 2005;22(5):343–356), we replicated local field potential recordings of hippocampal rat slices with and without stimulation. Through an automated comparison of simulated and real data segments, we classified different types of epileptic activity and estimated levels of excitatory and inhibitory synaptic gains across time. Result: Spontaneous transitions from interictal to ictal activity were associated with consistent patterns of excitatory and inhibitory dynamics. Interestingly, model results suggest that an increase of excitation close to seizure onset is preceded by a slow build-up of peri-dendritic inhibition. Single pulse stimulation with varying intensity led to seizure facilitation, accompanied by a significant increase in excitation pre-to-post stimulation. Repetitive stimulation at 1 Hz with varying intensity and duration led to seizure prevention, locking synaptic communication to a characteristic state post stimulation. During stimulation, we observed an increase of excitation, followed by a drop in somatic and an increase in dendritic inhibition, prolonging the duration of the inter-seizure interval. Conclusion: A slow build-up of dendritic inhibition might be linked to ictogenesis. Opposing effects of brain stimulation are associated with characteristic changes in synaptic transmission.

Aberrant neuronal connectivity in the cortex drives generation of seizures in rat absence epilepsy.

Absence epilepsy belongs to genetic epilepsies and is characterized by recurrent generalized seizures that are concomitant with alterations of consciousness and associated with cognitive comorbidities. Little is known about the mechanisms leading to occurrence of epileptic seizures (i.e. epileptogenesis) and, in particular, it remains an open question as to whether neuronal hypersynchronization, a key feature in seizure initiation, could result from aberrant structural connectivity within neuronal networks endowing them with epileptic properties. In the present study, we addressed this question using a genetic model of absence epilepsy in the rat where seizures initiate in the whisker primary somatosensory cortex (wS1). We hypothesized that alterations in structural connectivity of neuronal networks within wS1 contribute to pathological neuronal synchronization responsible for seizures. First, we used rabies virus-mediated retrograde synaptic tracing and showed that cortical neurons located in both upper- and deep-layers of wS1 displayed aberrant and significantly increased connectivity in the genetic model of absence epilepsy, as highlighted by a higher number of presynaptic partners. Next, we showed at the functional level that disrupting these aberrant wS1 neuronal networks with synchrotron X-ray-mediated cortical microtransections drastically decreased both the synchronization and seizure power of wS1 neurons, as revealed by in vivo local field potential recordings with multichannel probes. Taken together, our data provide for the first time strong evidence that increased structural connectivity patterns of cortical neurons represent critical pathological substrates for increased neuronal synchronization and generation of absence seizures.

Differentiation of speech-induced artifacts from physiological high gamma activity in intracranial recordings

There is great interest in identifying the neurophysiological underpinnings of speech production. Deep brain stimulation (DBS) surgery is unique in that it allows intracranial recordings from both cortical and subcortical regions in patients who are awake and speaking. The quality of these recordings, however, may be affected to various degrees by mechanical forces resulting from speech itself. Here we describe the presence of speech-induced artifacts in local-field potential (LFP) recordings obtained from mapping electrodes, DBS leads, and cortical electrodes. In addition to expected physiological increases in high gamma (60–200 Hz) activity during speech production, time-frequency analysis in many channels revealed a narrowband gamma component that exhibited a pattern similar to that observed in the speech audio spectrogram. This component was present to different degrees in multiple types of neural recordings. We show that this component tracks the fundamental frequency of the participant's voice, correlates with the power spectrum of speech and has coherence with the produced speech audio. A vibration sensor attached to the stereotactic frame recorded speech-induced vibrations with the same pattern observed in the LFPs. No corresponding component was identified in any neural channel during the listening epoch of a syllable repetition task. These observations demonstrate how speech-induced vibrations can create artifacts in the primary frequency band of interest. Identifying and accounting for these artifacts is crucial for establishing the validity and reproducibility of speech-related data obtained from intracranial recordings during DBS surgery.

Local Field Potential-Based Programming: A Proof-of-Concept Pilot Study

ObjectivesProgramming deep brain stimulation (DBS) is still based on a trial-and-error approach, often becoming a time-consuming process for both treating physicians and patients. Several strategies have been proposed to streamline DBS programming, most of which are preliminary and mainly address Parkinson's disease, a condition readily responsive to DBS adjustments. In the present proof-of-principle pilot study, we successfully demonstrate that local field potential (LFP)-based programming can be an effective approach when used for DBS indications that have a delayed temporal onset of benefit. Materials and MethodsA recently commercialized implantable pulse generator (IPG) with the capability to non-invasively and chronically stream live and/or record LFPs from a DBS electrode after implantation was used to program one pediatric patient with generalized dystonia and an adult with seizures refractory to multiple medications and vagal nerve stimulation. ResultsThe IPG survey function detected a peak in the delta range (1.95 Hz) in the left globus pallidus of the first patient. This LFP was detected when recording in the brain area adjacent to contacts 9 and 10 and absent when recording from other areas. The chronic recording of the 1.95 Hz LFP with two sets of stimulation showed a greater power increase with the settings associated with a worsening of dystonia. Broadband LFP home recording of “absence seizure” and “focal/partial seizure” was used in the second patient and reviewer with the IPG “timeline” and “event” functions. The chronic recording of the 2.93 Hz and 8.79 Hz (spit sensing) showed a reduced power with the stimulation setting associated with seizure control. ConclusionsThe approach presented in this pilot proof-of-concept study may inform and streamline the DBS programming for conditions requiring clinicians and patients to wait weeks before appreciating any clinical benefit. Prospective studies on larger samples of patients are warranted.

Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex.

Recent advances in multi-electrode array technology have made it possible to monitor large neuronal ensembles at cellular resolution in animal models. In humans, however, current approaches restrict recordings to a few neurons per penetrating electrode or combine the signals of thousands of neurons in local field potential (LFP) recordings. Here we describe a new probe variant and set of techniques that enable simultaneous recording from over 200 well-isolated cortical single units in human participants during intraoperative neurosurgical procedures using silicon Neuropixels probes. We characterized a diversity of extracellular waveforms with eight separable single-unit classes, with differing firing rates, locations along the length of the electrode array, waveform spatial spread and modulation by LFP events such as inter-ictal discharges and burst suppression. Although some challenges remain in creating a turnkey recording system, high-density silicon arrays provide a path for studying human-specific cognitive processes and their dysfunction at unprecedented spatiotemporal resolution.

Dataset of human intracranial recordings during famous landmark identification

For most people, recalling information about familiar items in a visual scene is an effortless task, but it is one that depends on coordinated interactions of multiple, distributed neural components. We leveraged the high spatiotemporal resolution of direct intracranial recordings to better delineate the network dynamics underpinning visual scene recognition. We present a dataset of recordings from a large cohort of humans while they identified images of famous landmarks (50 individuals, 52 recording sessions, 6,775 electrodes, 6,541 trials). This dataset contains local field potential recordings derived from subdural and penetrating electrodes covering broad areas of cortex across both hemispheres. We provide this pre-processed data with behavioural metrics (correct/incorrect, response times) and electrode localisation in a population-normalised cortical surface space. This rich dataset will allow further investigation into the spatiotemporal progression of multiple neural processes underlying visual processing, scene recognition and cued memory recall.

Delta Oscillations Coordinate Intracerebellar and Cerebello-Hippocampal Network Dynamics during Sleep.

During sleep, the widespread coordination of neuronal oscillations across both cortical and subcortical brain regions is thought to support various physiological functions. However, how sleep-related activity within the brain's largest sensorimotor structure, the cerebellum, is multiplexed with well-described sleep-related mechanisms in regions such as the hippocampus remains unknown. We therefore simultaneously recorded from the dorsal hippocampus and three distinct regions of the cerebellum (Crus I, lobule VI, and lobules II/III) in male mice during natural sleep. Local field potential (LFP) oscillations were found to be coordinated between these structures in a sleep stage-specific manner. During non-REM sleep, prominent δ frequency coherence was observed between lobule VI and hippocampus, whereas non-REM-associated hippocampal sharp-wave ripple activity evoked discrete LFP modulation in all recorded cerebellar regions, with the shortest latency effects in lobule VI. We also describe discrete phasic sharp potentials (PSPs), which synchronize across cerebellar regions and trigger sharp-wave ripple suppression. During REM, cerebellar δ phase significantly modulated hippocampal theta frequency, and this effect was greatest when PSPs were abundant. PSPs were phase-locked to cerebellar δ oscillation peak and hippocampal theta oscillation trough, respectively. Within all three cerebellar regions, prominent LFP oscillations were observed at both low (δ, <4 Hz) and very high frequencies (∼250 Hz) during non-REM and REM sleep. Intracerebellar cross-frequency analysis revealed that δ oscillations modulate those in the very high-frequency range. Together, these results reveal multiple candidate physiological mechanisms to support "offline," bidirectional interaction within distributed cerebello-hippocampal networks.SIGNIFICANCE STATEMENT Sleep is associated with widespread coordination of activity across a range of brain regions. However, little is known about how activity within the largest sensorimotor region of the brain, the cerebellum, is both intrinsically organized and links with higher-order structures, such as the hippocampus, during sleep. By making multisite local field potential recordings in naturally sleeping mice, we reveal and characterize multiple sleep stage-specific physiological mechanisms linking three distinct cerebellar regions with the hippocampus. Central to these physiological mechanisms is a prominent δ (<4 Hz) oscillation, which temporally coordinates both intracerebellar and cerebello-hippocampal network dynamics. Understanding this distributed network activity is important for gaining insight into cerebellar contributions to sleep-dependent processes, such as memory consolidation.

Activity-State Dependent Reversal of Ketamine-Induced Resting State EEG Effects by Clozapine and Naltrexone in the Freely Moving Rat.

Ketamine is a non-competitive N-Methyl-D-aspartate receptor (NMDAR) antagonist used in the clinic to initiate and maintain anaesthesia; it induces dissociative states and has emerged as a breakthrough therapy for major depressive disorder. Using local field potential recordings in freely moving rats, we studied resting state EEG profiles induced by co-administering ketamine with either: clozapine, a highly efficacious antipsychotic; or naltrexone, an opioid receptor antagonist reported to block the acute antidepressant effects of ketamine. As human electroencephalography (EEG) is predominantly recorded in a passive state, head-mounted accelerometers were used with rats to determine active and passive states at a high temporal resolution to offer the highest translatability. In general, pharmacological effects for the three drugs were more pronounced in (or restricted to) the passive state. Specifically, during inactive periods clozapine induced increases in delta (0.1–4 Hz), gamma (30–60 Hz) and higher frequencies (>100 Hz). Importantly, it reversed the ketamine-induced reduction in low beta power (10–20 Hz) and potentiated ketamine-induced increases in gamma and high frequency oscillations (130–160 Hz). Naltrexone inhibited frequencies above 50 Hz and significantly reduced the ketamine-induced increase in high frequency oscillations. However, some frequency band changes, such as clozapine-induced decreases in delta power, were only seen in locomoting rats. These results emphasise the potential in differentiating between activity states to capture drug effects and translate to human resting state EEG. Furthermore, the differential reversal of ketamine-induced EEG effects by clozapine and naltrexone may have implications for the understanding of psychotomimetic as well as rapid antidepressant effects of ketamine.

People With Parkinson's Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles.

ObjectiveFreezing of gait is detrimental to patients with idiopathic Parkinson’s disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity.MethodsWe analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in ‘regular gait’ and during the ‘freezing’ episodes.ResultsIn stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing.ConclusionWe found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.

Parvalbumin expressing interneurons control spike-phase coupling of hippocampal cells to theta oscillations

Encoding of information by hippocampal neurons is defined by the number and the timing of action potentials generated relative to ongoing network oscillations in the theta (5–14 Hz), gamma (30–80 Hz) and ripple frequency range (150–200 Hz). The exact mechanisms underlying the temporal coupling of action potentials of hippocampal cells to the phase of rhythmic network activity are not fully understood. One critical determinant of action potential timing is synaptic inhibition provided by a complex network of Gamma-amino-hydroxy-butyric acid releasing (GABAergic) interneurons. Among the various GABAergic cell types, particularly Parvalbumin-expressing cells are powerful regulators of neuronal activity. Here we silenced Parvalbumin-expressing interneurons in hippocampal areas CA1 and the dentate gyrus in freely moving mice using the optogenetic silencing tool eNpHR to determine their influence on spike timing in principal cells. During optogenetic inhibition of Parvalbumin-expressing cells, local field potential recordings revealed no change in power or frequency of CA1 or dentate gyrus network oscillations. However, CA1 pyramidal neurons exhibited significantly reduced spike-phase coupling to CA1 theta, but not gamma or ripple oscillations. These data suggest that hippocampal Parvalbumin-expressing interneurons are particularly important for an intact theta-based temporal coding scheme of hippocampal principal cell populations.

High-Frequency Head Impact Disrupts Hippocampal Neural Ensemble Dynamics.

We have recently shown that the cognitive impairments in a mouse model of high-frequency head impact (HFHI) are caused by chronic changes to synaptic physiology. To better understand these synaptic changes occurring after repeat head impact, we used Thy1-GcCAMP6f mice to study intracellular and intercellular calcium dynamics and neuronal ensembles in HFHI mice. We performed simultaneous calcium imaging and local field potential (LFP) recordings of the CA1 field during an early-LTP paradigm in acute hippocampal slice preparations 24 h post-impact. As previously reported, HFHI causes a decrease in early-LTP in the absence of any shift in the input-output curve. Calcium analytics revealed that HFHI hippocampal slices have similar numbers of active ROIs, however, the number of calcium transients per ROI was significantly increased in HFHI slices. Ensembles consist of coordinated activity between groups of active ROIs. We exposed the CA1 ensemble to Schaffer-collateral stimulation in an abbreviated LTP paradigm and observed novel coordinated patterns of post stimulus calcium ensemble activity. HFHI ensembles displayed qualitatively similar patterns of post-stimulus ensemble activity to shams but showed significant changes in quantitative ensemble inactivation and reactivation. Previous in vivo and in vitro reports have shown that ensemble activity frequently occurs through a similar set of ROIs firing in a repeating fashion. HFHI slices showed a decrease in such coordinated firing patterns during post stimulus ensemble activity. The present study shows that HFHI alters synaptic activity and disrupts neuronal organization of the ensemble, providing further evidence of physiological synaptic adaptation occurring in the brain after a high frequency of non-pathological head impacts.

Reorganization of CA1 dendritic dynamics by hippocampal sharp-wave ripples during learning

The hippocampus plays a critical role in memory consolidation, mediated by coordinated network activity during sharp-wave ripple (SWR) events. Despite the link between SWRs and hippocampal plasticity, little is known about how network state affects information processing in dendrites, the primary sites of synaptic input integration and plasticity. Here, we monitored somatic and basal dendritic activity in CA1 pyramidal cells in behaving mice using longitudinal two-photon calcium imaging integrated with simultaneous local field potential recordings. We found immobility was associated with an increase in dendritic activity concentrated during SWRs. Coincident dendritic and somatic activity during SWRs predicted increased coupling during subsequent exploration of a novel environment. In contrast, somatic-dendritic coupling and SWR recruitment varied with cells' tuning distance to reward location during a goal-learning task. Our results connect SWRs with the stabilization of information processing within CA1 neurons and suggest that these mechanisms may be dynamically biased by behavioral demands.

Edge detections of MER Signals of STN with DBS micro electrode local field potential acquisitions in Parkinson`s

Deep brain stimulation of the subthalamic nucleus (STN) is a highly effective treatment for motor symptoms of Parkinson’s disease. Sub thalamic nucleus deep brain stimulation (STN-DBS) is a therapeutic surgical procedure for reducing the symptoms Parkinson’s and restoring and increasing the motor functioning. However, precise intraoperative edge or perimeter detection of STN remains a procedural challenge. In this study, we present the micro electrode signals recordings (MER) of STNs and local field potentials (LFPs) were acquired from deep brain stimulation macro electrodes during trajectory towards STN, in Parkinson patients. The frequency versus intensity atlas of field potential activity was obtained and further than investigated in distinct sub band’s, to explore whether field potentials activity can be employed for STN edge detection. STN perimeter detections by means of L F Ps were evaluated to edge predictions by way of the functional stereotactic DBS neurosurgeon, based on micro electrode derived, single unit recordings (M E R – S N A of S T Ns). The findings show variation amongst M E R – S N A and macro electrode L F P-signals gathering through MER-system pertaining to the d o r s a l S T N b o r d e r of -1.00±0.85mm plus -0.42±1.08 mm in the and frequencies, correspondingly. For these sub band`s, root mean square of the voids was found to be 1.27milli meters and 1.07milli meters. The Assessment of other sub band`s didn`t set a limit for differentiating the posterior (c a u d a l) point of sub-thalamic nuclei. We may infer that In conclusion, macro electrode signal acquisitions of STNs derived L F P gatherings might offer an unconventional methodology in the direction of m e r – s n a, for detecting the aimed target subthalamic nucleus borders during DBS-surgery.

Long-term in vivo application of a potassium channel-based optogenetic silencer in the healthy and epileptic mouse hippocampus

BackgroundOptogenetic tools allow precise manipulation of neuronal activity via genetically encoded light-sensitive proteins. Currently available optogenetic inhibitors are not suitable for prolonged use due to short-lasting photocurrents, tissue heating, and unintended changes in ion distributions, which may interfere with normal neuron physiology. To overcome these limitations, a novel potassium channel-based optogenetic silencer, named PACK, was recently developed. The PACK tool has two components: a photoactivated adenylyl cyclase from Beggiatoa (bPAC) and a cAMP-dependent potassium channel, SthK, which carries a large, long-lasting potassium current in mammalian cells. Previously, it has been shown that activating the PACK silencer with short light pulses led to a significant reduction of neuronal firing in various in vitro and acute in vivo settings. Here, we examined the viability of performing long-term studies in vivo by looking at the inhibitory action and side effects of PACK and its components in healthy and epileptic adult male mice.ResultsWe targeted hippocampal cornu ammonis (CA1) pyramidal cells using a viral vector and enabled illumination of these neurons via an implanted optic fiber. Local field potential (LFP) recordings from CA1 of freely moving mice revealed significantly reduced neuronal activity during 50-min intermittent (0.1 Hz) illumination, especially in the gamma frequency range. Adversely, PACK expression in healthy mice induced chronic astrogliosis, dispersion of pyramidal cells, and generalized seizures. These side effects were independent of the light application and were also present in mice expressing bPAC without the potassium channel. Light activation of bPAC alone increased neuronal activity, presumably via enhanced cAMP signaling. Furthermore, we applied bPAC and PACK in the contralateral hippocampus of chronically epileptic mice following a unilateral injection of intrahippocampal kainate. Unexpectedly, the expression of bPAC in the contralateral CA1 area was sufficient to prevent the spread of spontaneous epileptiform activity from the seizure focus to the contralateral hippocampus.ConclusionOur study highlights the PACK tool as a potent optogenetic inhibitor in vivo. However, further refinement of its light-sensitive domain is required to avoid unexpected physiological changes.