Local Field Potential Power Research Articles

Effects of neck proprioceptive modulation on pallidal network connectivity in dystonia.

Cervical dystonia (CD) is the third most common movement disorder affecting 1 million people worldwide. Proprioceptive modulation is the hallmark of contemporary therapies for dystonia, but the mechanism for this intervention is unclear. We studied proprioceptive influence on CD by measuring the spontaneous single-neuron responses and local field potentials (LFP) from the globus pallidus interna (GPi) in 17 CD patients (9 isolated CD and 8 with CD as a feature of generalized dystonia). The goal was to examine how high-frequency neck vibration, a putative modulator of neck proprioception changes pallidal physiology. We found that the neck vibration instantaneously alters the pallidal single neuron activity. We also found that neck vibration modulates pallido-cerebellar connectivity by changing alpha band in LFP recordings. The effects were more robust in those with isolated CD. The vibration also affects pallido-hippocampal connectivity by modulating theta-band power. These effects were more robust in CD with generalized dystonia. Vibration changed LFP only in select pallidal regions. Regions where LFP power was substantially modulated had a prominent proportion of burst subtypes of neurons, compared to pause or tonic subtypes. Such disparity in subtype was absent in regions where the LFP power was not modulated or subtly reduced with neck vibration. When changes in the theta, alpha and beta bands of the LFP recordings were compared against each other in response to vibration, high correlation was observed.

Prelimbic cortex and nucleus accumbens core resting state signaling dynamics as a biomarker for cocaine seeking behaviors

Substance use disorders (SUDs) are characterized by maladaptive signaling in the prefrontal cortex and associated regions, however precisely how these drug-induced abnormalities may be linked to drug seeking/taking behaviors is not well understood. Here, in vivo local field potential (LFP) electrophysiology was used in rats to examine the relationship between overall spontaneous (resting state) activity within the prelimbic cortex (PrL) and nucleus accumbens (NAc) core, and their functional connectivity, to cocaine taking and seeking behaviors. Adult, male Sprague-Dawley rats were trained to self-administer either intravenous cocaine (0.33 mg/inf) or water reinforcement during 6-hour daily sessions over 2 weeks; extinction sessions were completed immediately after self-administration training and following 30 days experimenter-imposed abstinence. Rest LFP recordings were completed during 3 recording periods (15 min each in a chamber different from the self-administration context) conducted (1) prior to self-administration training (rest LFP 1) (2) immediately after 2 weeks of self-administration training (rest LFP 2) and (3) following 1 month abstinence (rest LFP 3). Our findings show that resting state LFP power in the PrL recorded prior to training (Rest LFP 1) was positively correlated with total cocaine intake and escalation of cocaine seeking at the beta frequency range. Immediately after self-administration training (Rest LFP 2) power in the NAc core at gamma frequency was negatively correlated with incubation of cocaine craving. For rats trained to self-administer water, no significant correlations were observed. Together, these findings show that resting state LFP at specific timepoints in the addiction cycle can serve as unique predictors (biomarkers) of cocaine use disorders.

Selective serotonin reuptake inhibitors suppress sharp wave ripples in the ventral hippocampus

Biased memory processing contributes to the development and exacerbation of depression, and thus could represent a potential therapeutic target for stress-induced mental disorders. Synchronized spikes in hippocampal neurons, corresponding to sharp wave ripples (SWRs), may play a crucial role in memory reactivation. In this study, we showed that the frequency of SWRs increased in the ventral hippocampus, but not in the dorsal hippocampus, after stress exposure. Administration of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine inhibited the generation of ventral hippocampal SWRs and reduced locomotor activity and local field potential power in the gamma bands. These results suggest that the antidepressant effects of SSRIs may be mediated by the suppression of ventral hippocampal SWRs.

Beta oscillations in monkey striatum encode reward prediction error signals.

Reward prediction error (RPE) signals are crucial for reinforcement learning and decision making as they quantify the mismatch between predicted and obtained rewards. RPE signals are encoded in the neural activity of multiple brain areas, such as midbrain dopaminergic neurons, prefrontal cortex and striatum. However, it remains unclear how these signals are expressed through anatomically and functionally distinct subregions of the striatum. In the current study, we examined to which extent RPE signals are represented across different striatal regions. To do so, we recorded local field potentials (LFPs) in sensorimotor, associative, and limbic striatal territories of two male rhesus monkeys performing a free-choice probabilistic learning task. The trial-by-trial evolution of RPE during task performance was estimated using a reinforcement learning model fitted on monkeys' choice behavior. Overall, we found that changes in beta-band oscillations (15-35 Hz), after the outcome of the animal's choice, are consistent with RPE encoding. Moreover, we provide evidence that the signals related to RPE are more strongly represented in the ventral (limbic) than dorsal (sensorimotor and associative) part of the striatum. To conclude, our results suggest a relationship between striatal beta oscillations and the evaluation of outcomes based on RPE signals and highlight a major contribution of the ventral striatum to the updating of learning processes.Significance StatementReward prediction error (RPE) signals are crucial for reinforcement learning and decision making as they quantify the mismatch between predicted and obtained rewards. Current models suggest that RPE signals are encoded in the neural activity of multiple brain areas, including the midbrain dopaminergic neurons, prefrontal cortex and striatum. However, it remains elusive whether RPEs recruit anatomically and functionally distinct subregions of the striatum. Our study provides evidence that RPE-related modulations in LFP power are dominant in the striatum. In particular, they are stronger in the rostro-ventral rather than the caudo-dorsal striatum. Our findings contribute to a better understanding of the role of striatal territories in reward-based learning and may be relevant for neuropsychiatric and neurological diseases that affect striatal circuits.

Serotonergic modulation of local network processing in V1 mirrors previously reported signatures of local network modulation by spatial attention.

Sensory processing is influenced by neuromodulators such as serotonin, thought to relay behavioural state. Recent work has shown that the modulatory effect of serotonin itself differs with the animal's behavioural state. In primates, including humans, the serotonin system is anatomically important in the primary visual cortex (V1). We previously reported that in awake fixating macaques, serotonin reduces the spiking activity by decreasing response gain in V1. But the effect of serotonin on the local network is unknown. Here, we simultaneously recorded single-unit activity and local field potentials (LFPs) while iontophoretically applying serotonin in V1 of alert monkeys fixating on a video screen for juice rewards. The reduction in spiking response we observed previously is the opposite of the known increase of spiking activity with spatial attention. Conversely, in the local network (LFP), the application of serotonin resulted in changes mirroring the local network effects of previous reports in macaques directing spatial attention to the receptive field. It reduced the LFP power and the spike-field coherence, and the LFP became less predictive of spiking activity, consistent with reduced functional connectivity. We speculate that together, these effects may reflect the sensory side of a serotonergic contribution to quiet vigilance: The lower gain reduces the salience of stimuli to suppress an orienting reflex to novel stimuli, whereas at the network level, visual processing is in a state comparable to that of spatial attention.

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

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

Intraoperative Local Field Potential Beta Power and Three-Dimensional Neuroimaging Mapping Predict Long-Term Clinical Response to Deep Brain Stimulation in Parkinson Disease: A Retrospective Study

BackgroundDirectional deep brain stimulation (DBS) leads allow a fine-tuning control of the stimulation field, however, this new technology could increase the DBS programming time because of the higher number of the possible combinations used in directional DBS than in standard nondirectional electrodes. Neuroimaging leads localization techniques and local field potentials (LFPs) recorded from DBS electrodes implanted in basal ganglia are among the most studied biomarkers for DBS programing. ObjectiveThis study aimed to evaluate whether intraoperative LFPs beta power and neuroimaging reconstructions correlate with contact selection in clinical programming of DBS in patients with Parkinson disease (PD). Materials and MethodsIn this retrospective study, routine intraoperative LFPs recorded from all contacts in the subthalamic nucleus (STN) of 14 patients with PD were analyzed to calculate the beta band power for each contact. Neuroimaging reconstruction obtained through Brainlab Elements Planning software detected contacts localized within the STN. Clinical DBS programming contact scheme data were collected after one year from the implant. Statistical analysis evaluated the diagnostic performance of LFPs beta band power and neuroimaging data for identification of the contacts selected with clinical programming. We evaluated whether the most effective contacts identified based on the clinical response after one year from implant were also those with the highest level of beta activity and localized within the STN in neuroimaging reconstruction. ResultsLFPs beta power showed a sensitivity of 67%, a negative predictive value (NPV) of 84%, a diagnostic odds ratio (DOR) of 2.7 in predicting the most effective contacts as evaluated through the clinical response. Neuroimaging reconstructions showed a sensitivity of 62%, a NPV of 77%, a DOR of 1.20 for contact effectivity prediction. The combined use of the two methods showed a sensitivity of 87%, a NPV of 87%, a DOR of 2.7 for predicting the clinically more effective contacts. ConclusionsThe combined use of LFPs beta power and neuroimaging localization and segmentations predict which are the most effective contacts as selected on the basis of clinical programming after one year from implant of DBS. The use of predictors in contact selection could guide clinical programming and reduce time needed for it.

Acute effects of deep brain stimulation on brain function in obsessive–compulsive disorder

ObjectiveDeep brain stimulation (DBS) is an effective treatment for refractory obsessive–compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD. MethodsWe explored how DBS doses between 3–5 V delivered to the ventral anterior limb of the internal capsule of five OCD patients affected electroencephalograms and intracranial local field potentials (LFPs). We focused on theta power/ phase-stability, given their previously established role in DBS for OCD. ResultsCortical theta power and theta phase-stability did not increase significantly with DBS voltage. DBS-induced theta power peaks were seen at the previously defined individualized therapeutic voltage. Although LFP power generally increased with DBS voltages, this occurred mostly in frequency peaks that overlapped with stimulation artifacts limiting its interpretability. Though highly idiosyncratic, three subjects showed significant acute DBS effects on electroencephalogram theta power and four subjects showed significant carry-over effects (pre-vs post DBS, unstimulated) on LFP and electroencephalogram theta power. ConclusionsOur findings challenge the presence of a consistent dose–response relationship between stimulation voltage and brain activity. SignificanceTheta power may be investigated further as a neurophysiological marker to aid personalized DBS voltage optimization in OCD.

Modulation effect of non-invasive transcranial ultrasound stimulation in an ADHD rat model

Objective. Previous studies have demonstrated that transcranial ultrasound stimulation (TUS) with noninvasive high penetration and high spatial resolution has an effective neuromodulatory effect on neurological diseases. Attention deficit hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that severely affects child health. However, the neuromodulatory effects of TUS on ADHD have not been reported to date. This study aimed to investigate the neuromodulatory effects of TUS on ADHD. Approach. TUS was performed in ADHD model rats for two consecutive weeks, and the behavioral improvement of ADHD, neural activity of ADHD from neurons and neural oscillation levels, and the plasma membrane dopamine transporter and brain-derived neurotrophic factor (BDNF) in the brains of ADHD rats were evaluated. Main results. TUS can improve cognitive behavior in ADHD rats, and TUS altered neuronal firing patterns and modulated the relative power and sample entropy of local field potentials in the ADHD rats. In addition, TUS can also enhance BDNF expression in the brain tissues. Significance. TUS has an effective neuromodulatory effect on ADHD and thus has the potential to clinically improve cognitive dysfunction in ADHD.

Neuromodulation in the developing visual cortex after long-term monocular deprivation.

Neural dynamics are altered in the primary visual cortex (V1) during critical period monocular deprivation (MD). Synchronization of neural oscillations is pertinent to physiological functioning of the brain. Previous studies have reported chronic disruption of V1 functional properties such as ocular dominance, spatial acuity, and binocular matching after long-term monocular deprivation (LTMD). However, the possible neuromodulation and neural synchrony has been less explored. Here, we investigated the difference between juvenile and adult experience-dependent plasticity in mice from intracellular calcium signals with fluorescent indicators. We also studied alterations in local field potentials power bands and phase-amplitude coupling (PAC) of specific brain oscillations. Our results showed that LTMD in juveniles causes higher neuromodulatory changes as seen by high-intensity fluorescent signals from the non-deprived eye (NDE). Meanwhile, adult mice showed a greater response from the deprived eye (DE). LTMD in juvenile mice triggered alterations in the power of delta, theta, and gamma oscillations, followed by enhancement of delta-gamma PAC in the NDE. However, LTMD in adult mice caused alterations in the power of delta oscillations and enhancement of delta-gamma PAC in the DE. These markers are intrinsic to cortical neuronal processing during LTMD and apply to a wide range of nested oscillatory markers.

The effects of betulinic acid chronic administration on the motor, non-motor behaviors, and globus pallidus local field potential power in a rat model of hemiparkinsonism.

Parkinson's disease (PD) is a neurodegenerative disorder involving the central nervous system associated with motor and non-motor impairments. Betulinic acid (BA) is a natural substance considered an antioxidative agent. This study aimed to investigate the therapeutic potential of BA on motor dysfunctions and globus pallidus (GP) local EEG power in a 6-hydroxydopamine (6-OHDA)-induced rat model of hemiparkinsonism. Adult Wistar rats were categorized into different groups, containing; Sham, PD, and treated groups including different doses of BA (0.5, 5, and 10 mg/kg, IP), and L-dopa (20 mg/kg, PO, as positive control). The lesion was induced in the right medial forebrain bundle by injection of 6-OHDA (20 µg/kg). The treatment was begun just after the approved rotational test induced by apomorphine, 14 days after 6-OHDA administration. Motor behaviors such as catalepsy and stride-length and non-motor responses, including GP local EEG, were then assessed. Also, the levels of GSH, catalase, and concentration of dopamine in the brain tissue were measured. Treatment of hemiparkinsonian rats with BA significantly improved catalepsy and stride-length (P<0.001 and P<0.01, respectively) and GP frequency bands' powers (P<0.001). Moreover, the activities of GSH (P<0.001), catalase (P<0.001), and the concentration of dopamine (P<0.001) in the brain were increased. Current results proved the potent ability of BA to scavenge free radicals and to remove oxidative agents in the brain tissue. This natural product could be considered a possible therapeutic compound for motor and non-motor disorders in PD.

Plasticity after cognitive training reflected in prefrontal local field potentials

SummaryLearning to perform a new cognitive task induces plasticity of the prefrontal cortex generally involving activation of more neurons and increases in firing rate; however, its effects on single neurons are diverse and complex. We sought to understand how training affects global measures of neural activity by recording and analyzing local field potentials (LFPs) in monkeys before and after they learned to perform working memory tasks. LFP power after training was characterized by a reduction in power in 20–40 Hz during the stimulus presentations and delay periods of the task. Both evoked power, synchronized to task events, and induced power exhibited this decrease after training. The effect was consistent across tasks requiring memory of spatial location and stimulus shape. Error trials were characterized by a lack of LFP power ramping around the fixation onset. Our results reveal signatures of cortical plasticity in LFPs associated with learning to perform cognitive tasks.

LiCl-induced sickness modulates rat gustatory cortical responses.

Gustatory cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animal's health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFPs) from healthy rats and rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in 7 to 12 Hz LFP power at approximately 12 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness-a result reflecting the collapse of responses toward a simple "good-bad" code visible in the entire sample, but focused on a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness' impact on consumption.

An ErbB4-Positive Neuronal Network in the Olfactory Bulb for Olfaction.

Olfactory information is relayed and processed in the olfactory bulb (OB). Mitral cells, the principal output excitatory neurons of the OB, are controlled by multiple types of interneurons. However, mechanisms that regulate the activity of OB interneurons are not well understood. We provide evidence that the transmembrane tyrosine kinase ErbB4 is selectively expressed in subsets of OB inhibitory neurons in both male and female mice. ErbB4-positive (ErbB4+) neurons are mainly located in the glomerular layer (GL) and granule cell layer (GCL) and do not express previously defined markers. Optogenetic activation of GL-ErbB4+ neurons promotes theta oscillation, whereas activation of those in the GCL generates γ oscillations. Stimulation of OB slices with NRG1, a ligand that activates ErbB4, increases GABA transmission onto mitral cells, suggesting a role of OB NRG1-ErbB4 signaling in olfaction. In accord, ErbB4 mutant mice or acute inhibition of ErbB4 by a chemical genetic approach diminishes GABA transmission, reduces bulbar local field potential power, increases the threshold of olfactory sensitivity, and impairs odor discrimination. Together, these results identified a bulbar inhibitory network of ErbB4+ neurons for olfaction. Considering that both Nrg1 and Erbb4 are susceptibility genes for neuropsychiatric disorders, our study provides insight into pathologic mechanisms of olfactory malfunctions in these disorders.SIGNIFICANCE STATEMENT This study demonstrates that ErbB4+ neurons are a new subset of olfactory bulb inhibitory neurons in the glomerular layer and granule cell layer that innervate mitral cells and ErbB4- cells. They regulate olfaction by controlling local synchrony and distinct oscillations. ErbB4 inhibition diminishes GABA transmission, reduces bulbar local field potential power, increases the threshold of olfactory sensitivity, and impairs odor discrimination. Our results provide insight into pathophysiological mechanism of olfaction deficits in brain disorders associated with Nrg1 or Erbb4 mutations.

Levodopa-dependent differences in the non-oscillatory activity of the subthalamic nucleus.

The study of local field potentials (LFP) recorded from the basal ganglia of patients with movement disorders led to significant advancement in the understanding the pathophysiology of Parkinson's disease (PD). The possibility of investigating possible changes in the activity of the brain caused by the levodopa administration may provide a useful tool to evaluate the influence or the side-effects of the treatment from patient to patient. The analysis was carried out through a systematic analysis of the fractal component of the subthalamic local field potentials (STN-LFP) that may reveal, with respect to the classical power spectrum analysis, novel important information about the dynamic modulation caused by the drug intake. Indeed, so far, much of what is known about that is related to the presence of a spectral peak in the beta frequency band then attenuated after the levodopa administration. The nonlinear power-law exponent goes beyond this feature, exploring differences that reflect the fractal (scale-free) behavior of the PD brain dynamics. Here, in order to demonstrate that the presence or absence of the peak has no effect on the computation of the power-law exponent, we used simulated LFP recordings. After that, we performed the fractal analysis in shorts epochs of STN LFPs recordings ( N=24 patients, 12 females and 12 males) before and after Levodopa administration. We found no differences in the nonlinear power-law exponent for simulated data, reinforcing the idea that the parameter was not influenced by the attenuation of the hallmark peak for PD patients. As regard real LFP time series, we found that pharmacological treatment for PD differently altered LFP power of non-oscillatory activity, as well as changed the level of fractal exponent in specific frequency bands. Particularly we observed an increase of the fractal exponent in condition of post-levodopa with significant differences related to the response to levodopa in Parkinson's disease. Clinical Relevance- This study points out a potentially novel non-oscillatory biomarker which could reflect intrinsic properties of complex biological systems thus constituting a potential target parameter for novel and alternative neuroprosthetic applications.

Inferior temporal cortex leads prefrontal cortex in response to a violation of a learned sequence.

Primates learn statistical regularities that are embedded in visual sequences, a form of statistical learning. Single-unit recordings in macaques showed that inferior temporal (IT) neurons are sensitive to statistical regularities in visual sequences. Here, we asked whether ventrolateral prefrontal cortex (VLPFC), which is connected to IT, is also sensitive to the transition probabilities in visual sequences and whether the statistical learning signal in IT originates in VLPFC. We recorded simultaneously multiunit activity (MUA) and local field potentials (LFPs) in IT and VLPFC after monkeys were exposed to triplets of images with a fixed presentation order. In both areas, the MUA was stronger to images that violated the learned sequence (deviants) compared to the same images presented in the learned triplets. The high-gamma and beta LFP power showed an enhanced and suppressed response, respectively, to the deviants in both areas. The enhanced response was present also for the image following the deviant, suggesting a sensitivity for temporal adjacent dependencies in IT and VLPFC. The increased response to the deviant occurred later in VLPFC than in IT, suggesting that the deviant response in IT was not inherited from VLPFC. These data support predictive coding theories that propose a feedforward flow of prediction errors.

A striatal SOM-driven ChAT-iMSN loop generates beta oscillations and produces motor deficits.

Enhanced beta oscillations within the cortico-basal ganglia-thalamic (CBT) network are correlated with motor deficits in Parkinson's disease (PD), whose generation has been associated recently with amplified network dynamics in the striatum. However, how distinct striatal cell subtypes interact to orchestrate beta oscillations remains largely unknown. Here, we show that optogenetic suppression of dopaminergic control over the dorsal striatum (DS) elevates the power of local field potentials (LFPs) selectively at beta band (12-25Hz), accompanied by impairments in locomotion. The amplified beta power originates from a striatal loop driven by somatostatin-expressing (SOM) interneurons and constituted by choline acetyltransferase (ChAT)-expressing interneurons and dopamine D2 receptor (D2R)-expressing medium spiny neurons (iMSNs). Moreover, closed-loop intervention selectively targeting striatal iMSNs or ChATs diminishes beta oscillations and restores motor function. Thus, we reveal a striatal microcircuit motif that underlies beta oscillation generation and accompanied motor deficits upon perturbation of dopaminergic control over the striatum.

Long Term Performance of a Bi-Directional Neural Interface for Deep Brain Stimulation and Recording.

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.Methods: Seven ovine subjects were implanted with deep brain stimulation (DBS) leads at different nodes within the Circuit of Papez: four with unilateral leads in the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® (Medtronic) or Percept PC°ledR (Medtronic) deep brain stimulation and recording device. Spontaneous local field potentials (LFPs), evoked potentials (EPs), LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up.

PtNPs/PEDOT:PSS-Modified Microelectrode Arrays Reveal Electrophysiological Activities of Different Neurons in Medial Amygdala of Mice Under Innate Fear.

The medial amygdala (MA) plays an important role in the innate fear circuit. However, the electrophysiological mechanism of MA for processing innate fear needs to be further explored. In this study, we fabricated microelectrode arrays (MEAs) with detecting sites arranged to match the location and shape of MA in mice and detected the electrophysiology in freely behaving mice under 2-methyl-2-thiazoline (2MT)-induced fear. The detection performance of MEA is improved by modifying metal nanoparticles and conductive polymers (PtNPs/PEDOT:PSS). After modification, the impedance magnitude and phase of electrodes were decreased to 27.0 ± 2.3 kΩ and −12.30 ± 0.52°, respectively, leading to a signal-to-noise ratio of 10. Its electrochemical stability and mechanical stability were also verified by cyclic voltammetry (CV) sweeping and ultrasonic vibration. MEAs were then implanted into the MA of mice, and the electrophysiology and behavioral characteristics were synchronously recorded and analyzed. The results showed that 2MT induced strong defensive behaviors in mice, accompanied by increases in the average spike firing rate and local field potential (LFP) power of MA neurons. According to principles commonly applied to cortical extracellular recordings, the recorded neurons are divided into two classes based on waveforms. Statistics showed that about 37% of type 1 neurons (putative GABAergic neurons) and 87% of type 2 neurons (putative glutamatergic neurons) were significantly activated under innate fear. At the same time, the firing rate of some activated neurons had a good linear correlation with the freezing rate.

Distinct ensembles in the noradrenergic locus coeruleus are associated with diverse cortical states

The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical “activated” cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased high-frequency power as well as other states including decreased high-frequency power. Thus—in contrast to the stereotypical activated brain state evoked by en masse LC stimulation—spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.