Local Field Potential Responses Research Articles

Late-adolescent onset of prefrontal endocannabinoid control of hippocampal and amygdalar inputs and its impact on trace-fear conditioning behavior.

Prefrontal cortex (PFC) maturation during adolescence is characterized by structural and functional changes, which involve the remodeling of GABA and glutamatergic synapses, as well as changes in the endocannabinoid system. Yet, the way PFC endocannabinoid signaling interacts with local GABA and glutamatergic function to impact its processing of afferent transmission during the adolescent transition to adulthood remains unknown. Here we combined PFC local field potential recordings with local manipulations of 2-AG and anandamide levels to assess how PFC endocannabinoid signaling is recruited to modulate ventral hippocampal and basolateral amygdalar inputs in vivo in adolescent and adult male rats. We found that the PFC endocannabinoid signaling does not fully emerge until late-adolescence/young adulthood. Once present, both 2-AG and anandamide can be recruited in the PFC to limit the impact of hippocampal drive through a CB1R-mediated mechanism whereas basolateral amygdalar inputs are only inhibited by 2-AG. Similarly, the behavioral effects of increasing 2-AG and anandamide in the PFC do not emerge until late-adolescence/young adulthood. Using a trace fear conditioning paradigm, we found that elevating PFC 2-AG levels preferentially reduced freezing behavior during acquisition without affecting its extinction. In contrast, increasing anandamide levels in the PFC selectively disrupted the extinction of trace fear memory without affecting its acquisition. Collectively, these results indicate a protracted recruitment of PFC endocannabinoid signaling, which becomes online in late adolescence/young adulthood as revealed by its impact on hippocampal and amygdalar-evoked local field potential responses and trace fear memory behavior.

Dysfunction of specific auditory fibers impacts cortical oscillations, driving an autism phenotype despite near-normal hearing.

Autism spectrum disorder is discussed in the context of altered neural oscillations and imbalanced cortical excitation-inhibition of cortical origin. We studied here whether developmental changes in peripheral auditory processing, while preserving basic hearing function, lead to altered cortical oscillations. Local field potentials (LFPs) were recorded from auditory, visual, and prefrontal cortices and the hippocampus of BdnfPax2 KO mice. These mice develop an autism-like behavioral phenotype through deletion of BDNF in Pax2+ interneuron precursors, affecting lower brainstem functions, but not frontal brain regions directly. Evoked LFP responses to behaviorally relevant auditory stimuli were weaker in the auditory cortex of BdnfPax2 KOs, connected to maturation deficits of high-spontaneous rate auditory nerve fibers. This was correlated with enhanced spontaneous and induced LFP power, excitation-inhibition imbalance, and dendritic spine immaturity, mirroring autistic phenotypes. Thus, impairments in peripheral high-spontaneous rate fibers alter spike synchrony and subsequently cortical processing relevant for normal communication and behavior.

Information content and temporal structure of face selective local field potentials frequency bands in IT cortex.

Sensory stimulation triggers synchronized bioelectrical activity in the brain across various frequencies. This study delves into network-level activities, specifically focusing on local field potentials as a neural signature of visual category representation. Specifically, we studied the role of different local field potential frequency oscillation bands in visual stimulus category representation by presenting images of faces and objects to three monkeys while recording local field potential from inferior temporal cortex. We found category selective local field potential responses mainly for animate, but not inanimate, objects. Notably, face-selective local field potential responses were evident across all tested frequency bands, manifesting in both enhanced (above mean baseline activity) and suppressed (below mean baseline activity) local field potential powers. We observed four different local field potential response profiles based on frequency bands and face selective excitatory and suppressive responses. Low-frequency local field potential bands (1-30Hz) were more prodominstaly suppressed by face stimulation than the high-frequency (30-170Hz) local field potential bands. Furthermore, the low-frequency local field potentials conveyed less face category informtion than the high-frequency local field potential in both enhansive and suppressive conditions. Furthermore, we observed a negative correlation between face/object d-prime values in all the tested local field potential frequency bands and the anterior-posterior position of the recording sites. In addition, the power of low-frequency local field potential systematically declined across inferior temporal anterior-posterior positions, whereas high-frequency local field potential did not exhibit such a pattern. In general, for most of the above-mentioned findings somewhat similar results were observed for body, but not, other stimulus categories. The observed findings suggest that a balance of face selective excitation and inhibition across time and cortical space shape face category selectivity in inferior temporal cortex.

A Cortical Mechanism Linking Saliency Detection and Motor Reactivity in Rhesus Monkeys.

Sudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two male rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFPs) recorded from the dorsolateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force, a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was symmetrical and maximal at the scalp vertex, highly reminiscent of the human "vertex potential." Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the LFPs recorded from deep rather than superficial cortical layers. These results disclose a phylogenetically preserved corticomotor mechanism supporting adaptive behavior in response to salient sensory events.Significance Statement Survival in the natural world depends on an animal's capacity to adapt ongoing behavior to abrupt unexpected events. To study the neural mechanisms underlying this capacity, we trained monkeys to apply constant force on a joystick while we recorded their brain activity from the scalp and the prefrontal cortex contralateral to the hand holding the joystick. Unexpected auditory stimuli elicited a biphasic force modulation: a transient reduction followed by a corrective adjustment. The same stimuli also elicited EEG and LFP responses, dominated by a biphasic wave that predicted the magnitude of the behavioral adjustment. These results disclose a phylogenetically preserved corticomotor mechanism supporting adaptive behavior in response to unexpected events.

Local field potential responses associated with perceptual filling-in at blind spot in macaque primary visual cortex.

To understand the neural mechanisms of perceptual filling-in at the blind spot (BS), we analyzed neural activity in the region representing the visual field corresponding to the BS (BS region) in the primary visual cortex (V1) of the macaque monkey. We inserted a linear array electrode into the BS region or surrounding region and recorded the multiunit activities (MUAs) and local field potential (LFP). We examined the responses of MUAs and LFP to a large visual stimulus that entirely covered the BS (surface stimuli) while the monkey performed a visual fixation task in either the monocular condition without receiving direct retinal input or the binocular condition receiving retinal information. We observed clear MUA responses in the deep layers within the BS region under monocular conditions, confirming previous reports that V1 neurons in the BS region are activated when perceptual filling-in occurs. Current source density analysis using LFP showed that MUA responses were mainly observed in layer 5. Although LFP responses were generally stronger in the binocular condition than in the monocular condition, a notable exception was observed in the BS region. LFP responses in the low-beta band in the superficial layers were stronger in the monocular condition than in the binocular condition. These results suggest that low-beta activity in the superficial layer is related to the occurrence of perceptual filling-in in the BS. The origin of this activity is considered to be feedback signals from the extrastriate areas to the V1.NEW & NOTEWORTHY Two characteristic activities were induced in the blind spot (BS) region in response to the stimulus, causing perceptual filling-in: 1) beta-band LFP responses in the superficial layers and 2) neuronal responses in the deep layers, mainly in layer 5. These data suggest that the feedback signal from the extrastriate areas to the BS region in V1 is involved in perceptual filling-in.

Optogenetic activation of visual thalamus generates artificial visual percepts.

The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFP) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz, and uncovered a striking phase locking between the V1 local field potential (LFP) and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

Initial case series of a novel sensing deep brain stimulation device in drug-resistant epilepsy and consistent identification of alpha/beta oscillatory activity: A feasibility study.

Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.

Somatosensory-Evoked Early Sharp Waves in the Neonatal Rat Hippocampus.

The developing entorhinal-hippocampal system is embedded within a large-scale bottom-up network, where spontaneous myoclonic movements, presumably via somatosensory feedback, trigger hippocampal early sharp waves (eSPWs). The hypothesis, that somatosensory feedback links myoclonic movements with eSPWs, implies that direct somatosensory stimulation should also be capable of evoking eSPWs. In this study, we examined hippocampal responses to electrical stimulation of the somatosensory periphery in urethane-anesthetized, immobilized neonatal rat pups using silicone probe recordings. We found that somatosensory stimulation in ~33% of the trials evoked local field potential (LFP) and multiple unit activity (MUA) responses identical to spontaneous eSPWs. The somatosensory-evoked eSPWs were delayed from the stimulus, on average, by 188 ms. Both spontaneous and somatosensory-evoked eSPWs (i) had similar amplitude of ~0.5 mV and half-duration of ~40 ms, (ii) had similar current-source density (CSD) profiles, with current sinks in CA1 strata radiatum, lacunosum-moleculare and DG molecular layer and (iii) were associated with MUA increase in CA1 and DG. Our results indicate that eSPWs can be triggered by direct somatosensory stimulations and support the hypothesis that sensory feedback from movements is involved in the association of eSPWs with myoclonic movements in neonatal rats.

ANet: Autoencoder-Based Local Field Potential Feature Extractor for Evaluating an Antidepressant Effect in Mice After Administering Kratom Leaf Extracts.

Kratom (KT) typically exerts antidepressant (AD) effects. However, evaluating which form of KT extracts possesses AD properties similar to the standard AD fluoxetine (flu) remained challenging. Here, we adopted an autoencoder (AE)-based anomaly detector called ANet to measure the similarity of mice's local field potential (LFP) features that responded to KT leave extracts and AD flu. The features that responded to KT syrup had the highest similarity to those that responded to the AD flu at 87.11 ± 0.25%. This finding presents the higher feasibility of using KT syrup as an alternative substance for depressant therapy than KT alkaloids and KT aqueous, which are the other candidates in this study. Apart from the similarity measurement, we utilized ANet as a multi-task AE and evaluated the performance in discriminating multi-class LFP responses corresponding to the effect of different KT extracts and AD flu simultaneously. Furthermore, we visualized learned latent features among LFP responses qualitatively and quantitatively as t-SNE projection and maximum mean discrepancy distance, respectively. The classification results reported the accuracy and F1-score of 90.11 ± 0.11% and 90.08 ± 0.00%. In summary, the outcomes of this research might help therapeutic design devices for an alternative substance profile evaluation, such as Kratom-based form, in real-world applications.

Differential Recovery of Submodality Touch Neurons and Interareal Communication in Sensory Input-Deprived Area 3b and S2 Cortices.

Cortical reactivation and regain of interareal functional connections have been linked to the recovery of hand grasping behavior after loss of sensory inputs in primates. We investigated contributions of neurons in two hierarchically organized somatosensory areas, 3b and S2, by characterizing local field potential (LFP) and multiunit spiking activity in five states (rest, stimulus-on, sustained, stimulus-off, and induced) and interareal communication after grasping behavior of dorsal column lesioned male squirrel monkeys had mostly recovered. Compared with normal cortex, fMRI, LFP, and spiking response magnitudes to step indentations were significantly weaker. The sustained component of the spiking recovered much better than the stimulus-off response. Correlation between overall spiking and γ LFP remained strong within each recovered areas 3b and S2. The interareal correlations of γ LFP were severely disrupted, except in the resting and stimulus-on periods. Interareal correlation of spiking was disrupted in the stimulus-off period only. In summary, submodality of low threshold mechanoreceptive neurons recovered differentially in input-deprived area 3b and S2 when impaired global hand grasping behavior returned. Slow-adapting-like neurons recovered, whereas rapid-adapting-like neurons did not. Interareal communications were also severely compromised. We propose that slow-adapting-like neurons and afferents in recovered area 3b and S2 mediate recovery of impaired grasping behavior after dorsal column tract lesion.SIGNIFICANCE STATEMENT Sensory feedback is essential for execution of hand grasping behavior in primates. Reactivations of somatosensory cortices have been attributed to recovery of such behavior after loss of sensory inputs via largely unknown mechanisms. In input-deprived area 3b and S2 cortex, after hand grasping behavior mostly recovered, we found slow-adapting-like neurons were greatly recovered, whereas rapid-adapting-like neurons did not. Communications between area 3b and S2 neurons were severely compromised. We suggest that recovery of slow-adapting-like neurons in input-deprived area 3b and S2 may mediate the recovery of hand grasping behavior.

Effects of optogenetic inhibition of a small fraction of parvalbumin-positive interneurons on the representation of sensory stimuli in mouse barrel cortex

Inhibitory interneurons play central roles in the modulation of spontaneous network activity and in processing of neuronal information. In sensory neocortical areas, parvalbumin-positive (PV+) GABAergic interneurons control the representation and processing of peripheral sensory inputs. We studied the functional role of PV+ interneurons in the barrel cortex of anesthetized adult PVCre mice by combining extracellular multi-electrode recordings with optogenetic silencing of a small fraction of PV+ interneurons. In all cortical layers, optogenetic inhibition caused an increase in spontaneous network activity from theta to gamma frequencies. The spatio-temporal representation of sensory inputs was studied by stimulating one or two whiskers at different intervals and analyzing the resulting local field potential (LFP) and single unit (SU) response. Silencing PV+ interneurons caused an increase in LFP response to sensory stimulation and a decrease in temporal discrimination of consecutive whisker deflections. The combined effect of whisker deflection and optogenetic inhibition was highly similar to the linear sum of the individual effects of these two manipulations. SU recordings revealed that optogenetic silencing reduced stimulus detectability by increasing stimulus-evoked firing rate by a constant offset, suggesting that PV+ interneurons improve signal-to-noise ratio by reducing ongoing spiking activity, thereby sharpening the spatio-temporal representation of sensory stimuli.

The impact of pulse timing on cortical and subthalamic nucleus deep brain stimulation evoked potentials.

The impact of pulse timing is an important factor in our understanding of how to effectively modulate the basal ganglia thalamocortical (BGTC) circuit. Single pulse low-frequency DBS-evoked potentials generated through electrical stimulation of the subthalamic nucleus (STN) provide insight into circuit activation, but how the long-latency components change as a function of pulse timing is not well-understood. We investigated how timing between stimulation pulses delivered in the STN region influence the neural activity in the STN and cortex. DBS leads implanted in the STN of five patients with Parkinson's disease were temporarily externalized, allowing for the delivery of paired pulses with inter-pulse intervals (IPIs) ranging from 0.2 to 10 ms. Neural activation was measured through local field potential (LFP) recordings from the DBS lead and scalp EEG. DBS-evoked potentials were computed using contacts positioned in dorsolateral STN as determined through co-registered post-operative imaging. We quantified the degree to which distinct IPIs influenced the amplitude of evoked responses across frequencies and time using the wavelet transform and power spectral density curves. The beta frequency content of the DBS evoked responses in the STN and scalp EEG increased as a function of pulse-interval timing. Pulse intervals <1.0 ms apart were associated with minimal to no change in the evoked response. IPIs from 1.5 to 3.0 ms yielded a significant increase in the evoked response, while those >4 ms produced modest, but non-significant growth. Beta frequency activity in the scalp EEG and STN LFP response was maximal when IPIs were between 1.5 and 4.0 ms. These results demonstrate that long-latency components of DBS-evoked responses are pre-dominantly in the beta frequency range and that pulse interval timing impacts the level of BGTC circuit activation.

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.

Altered cortical processing of sensory input in Huntington disease mouse models

Huntington disease (HD), a hereditary neurodegenerative disorder, manifests as progressively impaired movement and cognition. Although early abnormalities of neuronal activity in striatum are well established in HD models, there are fewer in vivo studies of the cortex. Here, we record local field potentials (LFPs) in YAC128 HD model mice versus wild-type mice. In multiple cortical areas, limb sensory stimulation evokes a greater change in LFP power in YAC128 mice. Mesoscopic imaging using voltage-sensitive dyes reveals more extensive spread of evoked sensory signals across the cortical surface in YAC128 mice. YAC128 layer 2/3 sensory cortical neurons ex vivo show increased excitatory events, which could contribute to enhanced sensory responses in vivo. Cortical LFP responses to limb stimulation, visual and auditory input are also significantly increased in zQ175 HD mice. Results presented here extend knowledge of HD beyond ex vivo studies of individual neurons to the intact cortical network.

Local Neuronal Responses to Intracortical Microstimulation in Rats' Barrel Cortex Are Dependent on Behavioral Context

The goal of cortical neuroprosthetics is to imprint sensory information as precisely as possible directly into cortical networks. Sensory processing, however, is dependent on the behavioral context. Therefore, a specific behavioral context may alter stimulation effects and, thus, perception. In this study, we reported how passive vs. active touch, i.e., the presence or absence of whisker movements, affects local field potential (LFP) responses to microstimulation in the barrel cortex in head-fixed behaving rats trained to move their whiskers voluntarily. The LFP responses to single-current pulses consisted of a short negative deflection corresponding to a volley of spike activity followed by a positive deflection lasting ~100 ms, corresponding to long-lasting suppression of spikes. Active touch had a characteristic effect on this response pattern. While the first phase including the negative peak remained stable, the later parts consisting of the positive peak were considerably suppressed. The stable phase varied systematically with the distance of the electrode from the stimulation site, pointing to saturation of neuronal responses to electrical stimulation in an intensity-dependent way. Our results suggest that modulatory effects known from normal sensory processing affect the response to cortical microstimulation as well. The network response to microstimulation is highly amenable to the behavioral state and must be considered for future approaches to imprint sensory signals into cortical circuits with neuroprostheses.

Ablation of microRNAs in VIP+ interneurons impairs olfactory discrimination and decreases neural activity in the olfactory bulb.

MicroRNAs (miRNAs) are abundantly expressed in vasoactive intestinal peptide expressing (VIP+ ) interneurons and are indispensable for their functional maintenance and survival. Here, we blocked miRNA biogenesis in postmitotic VIP+ interneurons in mice by selectively ablating Dicer, an enzyme essential for miRNA maturation, to study whether ablation of VIP+ miRNA affects olfactory function and neural activity in olfactory centres such as the olfactory bulb, which contains a large number of VIP+ interneurons. A go/no-go odour discrimination task and a food-seeking test were used to assess olfactory discrimination and olfactory detection. In vivo electrophysiological techniques were used to record single units and local field potentials. Olfactory detection and olfactory discrimination behaviours were impaired in VIP+ -specific Dicer-knockout mice. In vivo electrophysiological recordings in awake, head-fixed mice showed that both spontaneous and odour-evoked firing rates were decreased in mitral/tufted cells in knockout mice. The power of ongoing and odour-evoked beta local field potentials response of the olfactory bulb and anterior piriform cortex were dramatically decreased. Furthermore, the coherence of theta oscillations between the olfactory bulb and anterior piriform cortex was decreased. Importantly, Dicer knockout restricted to olfactory bulb VIP+ interneurons recapitulated the behavioural and electrophysiological results of the global knockout. VIP+ miRNAs are an important factor in sensory processing, affecting olfactory function and olfactory neural activity.

Sensory feedback-dependent coding of arm position in local field potentials of the posterior parietal cortex

Although multisensory integration is crucial for sensorimotor function, it is unclear how visual and proprioceptive sensory cues are combined in the brain during motor behaviors. Here we characterized the effects of multisensory interactions on local field potential (LFP) activity obtained from the superior parietal lobule (SPL) as non-human primates performed a reaching task with either unimodal (proprioceptive) or bimodal (visual-proprioceptive) sensory feedback. Based on previous analyses of spiking activity, we hypothesized that evoked LFP responses would be tuned to arm location but would be suppressed on bimodal trials, relative to unimodal trials. We also expected to see a substantial number of recording sites with enhanced beta band spectral power for only one set of feedback conditions (e.g. unimodal or bimodal), as was previously observed for spiking activity. We found that evoked activity and beta band power were tuned to arm location at many individual sites, though this tuning often differed between unimodal and bimodal trials. Across the population, both evoked and beta activity were consistent with feedback-dependent tuning to arm location, while beta band activity also showed evidence of response suppression on bimodal trials. The results suggest that multisensory interactions can alter the tuning and gain of arm position-related LFP activity in the SPL.

Limited Evidence for Sensory Prediction Error Responses in Visual Cortex of Macaques and Humans.

A recent formulation of predictive coding theory proposes that a subset of neurons in each cortical area encodes sensory prediction errors, the difference between predictions relayed from higher cortex and the sensory input. Here, we test for evidence of prediction error responses in spiking responses and local field potentials (LFP) recorded in primary visual cortex and area V4 of macaque monkeys, and in complementary electroencephalographic (EEG) scalp recordings in human participants. We presented a fixed sequence of visual stimuli on most trials, and violated the expected ordering on a small subset of trials. Under predictive coding theory, pattern-violating stimuli should trigger robust prediction errors, but we found that spiking, LFP and EEG responses to expected and pattern-violating stimuli were nearly identical. Our results challenge the assertion that a fundamental computational motif in sensory cortex is to signal prediction errors, at least those based on predictions derived from temporal patterns of visual stimulation.

Phasic oxygen dynamics confounds fast choline-sensitive biosensor signals in the brain of behaving rodents.

Cholinergic fast time-scale modulation of cortical physiology is critical for cognition, but direct local measurement of neuromodulators in vivo is challenging. Choline oxidase (ChOx)-based electrochemical biosensors have been used to capture fast cholinergic signals in behaving animals. However, these transients might be biased by local field potential and O2-evoked enzymatic responses. Using a novel Tetrode-based Amperometric ChOx (TACO) sensor, we performed highly sensitive and selective simultaneous measurement of ChOx activity (COA) and O2. In vitro and in vivo experiments, supported by mathematical modeling, revealed that non-steady-state enzyme responses to O2 give rise to phasic COA dynamics. This mechanism accounts for most of COA transients in the hippocampus, including those following locomotion bouts and sharp-wave/ripples. Our results suggest that it is unfeasible to probe phasic cholinergic signals under most behavioral paradigms with current ChOx biosensors. This confound is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.

Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body

BackgroundSystemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus.MethodsWe implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB).ResultsWe found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801.ConclusionOur data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.