Components Of Field Potentials Research Articles

Aperiodic components of local field potentials reflect inherent differences between cortical and subcortical activity.

The aperiodic component of local field potentials can be modeled to produce useful and reproducible indices of neural activity. Here we refined a widely used phenomenological model for extracting aperiodic parameters (namely the exponent, offset and knee), with which we fit cortical, basal ganglia, and thalamic intracranial local field potentials, recorded from unique cohorts of movement disorders and epilepsy patients. We found that the aperiodic exponent in motor cortex is higher in Parkinson's disease patients with more severe motor symptoms, suggesting that aperiodic features may have potential as electrophysiological biomarkers for movement disorders symptoms. Remarkably, we found conspicuous differences in the aperiodic parameters of basal ganglia and thalamic signals compared to those from neocortex.

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.

Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

Electrophysiological biomarkers reflecting the pathological activities in the basal ganglia are essential to gain an etiological understanding of Parkinson's disease (PD) and develop a method of diagnosing and treating the disease. Previous studies that explored electrophysiological biomarkers in PD have focused mainly on oscillatory or periodic activities such as beta and gamma oscillations. Emerging evidence has suggested that the nonoscillatory, aperiodic component reflects the firing rate and synaptic current changes corresponding to cognitive and pathological states. Nevertheless, it has never been thoroughly examined whether the aperiodic component can be used as a biomarker that reflects pathological activities in the basal ganglia in PD. In this study, we examined the parameters of the aperiodic component in hemiparkinsonian rats and tested its practicality as an electrophysiological biomarker of pathological activity. We found that a set of aperiodic parameters, aperiodic offset and exponent, were significantly decreased by the nigrostriatal lesion. To further prove the usefulness of the parameters as biomarkers, acute levodopa treatment reverted the aperiodic offset. We then compared the aperiodic parameters with a previously established periodic biomarker of PD, beta frequency oscillation. We found a significantly low negative correlation with beta power. We showed that the performance of the machine learning-based prediction of pathological activities in the basal ganglia can be improved by using both beta power and the aperiodic component, which showed a low correlation with each other. We suggest that the aperiodic component will provide a more sensitive measurement to early diagnosis PD and have the potential to use as the feedback parameter for the adaptive deep brain stimulation.

Broadband Dynamics Rather than Frequency-Specific Rhythms Underlie Prediction Error in the Primate Auditory Cortex.

Detection of statistical irregularities, measured as a prediction error response, is fundamental to the perceptual monitoring of the environment. We studied whether prediction error response is associated with neural oscillations or asynchronous broadband activity. Electrocorticography was conducted in three male monkeys, who passively listened to the auditory roving oddball stimuli. Local field potentials (LFPs) recorded over the auditory cortex underwent spectral principal component analysis, which decoupled broadband and rhythmic components of the LFP signal. We found that the broadband component captured the prediction error response, whereas none of the rhythmic components were associated with statistical irregularities of sounds. The broadband component displayed more stochastic, asymmetrical multifractal properties than the rhythmic components, which revealed more self-similar dynamics. We thus conclude that the prediction error response is captured by neuronal populations generating asynchronous broadband activity, defined by irregular dynamic states, which, unlike oscillatory rhythms, appear to enable the neural representation of auditory prediction error response.SIGNIFICANCE STATEMENT This study aimed to examine the contribution of oscillatory and asynchronous components of auditory local field potentials in the generation of prediction error responses to sensory irregularities, as this has not been directly addressed in the previous studies. Here, we show that mismatch negativity-an auditory prediction error response-is driven by the asynchronous broadband component of potentials recorded in the auditory cortex. This finding highlights the importance of nonoscillatory neural processes in the predictive monitoring of the environment. At a more general level, the study demonstrates that stochastic neural processes, which are often disregarded as neural noise, do have a functional role in the processing of sensory information.

New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat

Methoxetamine (MXE) is a dissociative substance of the arylcyclohexylamine class that has been present on the designer drug market as a ketamine-substitute since 2010. We have previously shown that MXE (i) possesses ketamine-like discriminative and positive rewarding effects in rats, (ii) affects brain processing involved in cognition and emotional responses, (iii) causes long-lasting behavioral abnormalities and neurotoxicity in rats and (iv) induces neurological, sensorimotor and cardiorespiratory alterations in mice. To shed light on the mechanisms through which MXE exerts its effects, we conducted a multidisciplinary study to evaluate the various neurotransmitter systems presumably involved in its actions on the brain. In vivo microdialysis study first showed that a single administration of MXE (0.25 and 0.5 mg/kg, i.v.) is able to significantly alter serotonin levels in the rat medial prefrontal cortex (mPFC) and nucleus accumbens. Then, we observed that blockade of the serotonin 5-HT2 receptors through two selective antagonists, ketanserin (0.1 mg/kg, i.p.) and MDL 100907 (0.03 mg/kg, i.p.), at doses not affecting animals behavior per se, attenuated the facilitatory motor effect and the inhibition on visual sensory responses induced by MXE (3 mg/kg, i.p.) and ketamine (3 mg/kg, i.p.), and prevented MXE-induced reduction of the prepulse inhibition in rats, pointing to the 5-HT2 receptors as a key target for the recently described MXE-induced sensorimotor effects. Finally, in-vitro electrophysiological studies revealed that the GABAergic and glutamatergic systems are also likely involved in the mechanisms through which MXE exerts its central effects since MXE inhibits, in a concentration-dependent manner, NMDA-mediated field postsynaptic potentials and GABA-mediated spontaneous currents. Conversely, MXE failed to alter both the AMPA component of field potentials and presynaptic glutamate release, and seems not to interfere with the endocannabinoid-mediated effects on mPFC GABAergic synapses. Altogether, our results support the notion of MXE as a NMDA receptor antagonist and shed further lights into the central mechanisms of action of this ketamine-substitute by pointing to serotonin 5-HT2 receptors as crucial players in the expression of its sensorimotor altering effects and to the NMDA and GABA receptors as potential further important targets of action.

Cross Laminar Traveling Components of Field Potentials due to Volume Conduction of Non-Traveling Neuronal Activity in Macaque Sensory Cortices.

Field potentials (FPs) reflect neuronal activities in the brain, and often exhibit traveling peaks across recording sites. While traveling FPs are interpreted as propagation of neuronal activity, not all studies directly reveal such propagating patterns of neuronal activation. Neuronal activity is associated with transmembrane currents that form dipoles and produce negative and positive fields. Thereby, FP components reverse polarity between those fields and have minimal amplitudes at the center of dipoles. Although their amplitudes could be smaller, FPs are never flat even around these reversals. What occurs around the reversal has not been addressed explicitly, although those are rationally in the middle of active neurons. We show that sensory FPs around the reversal appeared with peaks traveling across cortical laminae in macaque sensory cortices. Interestingly, analyses of current source density did not depict traveling patterns but lamina-delimited current sinks and sources. We simulated FPs produced by volume conduction of a simplified 2 dipoles' model mimicking sensory cortical laminar current source density components. While FPs generated by single dipoles followed the temporal patterns of the dipole moments without traveling peaks, FPs generated by concurrently active dipole moments appeared with traveling components in the vicinity of dipoles by superimposition of individually non-traveling FPs generated by single dipoles. These results indicate that not all traveling FP are generated by traveling neuronal activity, and that recording positions need to be taken into account to describe FP peak components around active neuronal populations.SIGNIFICANCE STATEMENT Field potentials (FPs) generated by neuronal activity in the brain occur with fields of opposite polarity. Likewise, in the cerebral cortices, they have mirror-imaged waveforms in upper and lower layers. We show that FPs appear like traveling across the cortical layers. Interestingly, the traveling FPs occur without traveling components of current source density, which represents transmembrane currents associated with neuronal activity. These seemingly odd findings are explained using current source density models of multiple dipoles. Concurrently active, non-traveling dipoles produce FPs as mixtures of FPs produced by individual dipoles, and result in traveling FP waveforms as the mixing ratio depends on the distances from those dipoles. The results suggest that not all traveling FP components are associated with propagating neuronal activity.

The dynamic properties of a brain network during working memory based on the algorithm of cross-frequency coupling.

Working memory (WM) refers to a memory system with limited energy for short-term maintenance and plays an important role in cognitive functions. At present, research regarding WM mostly focuses on the coordination between neural signals in the signal microelectrode channel. However, how neural signals coordinate the coding of WM at the network level is rarely studied. Cross-frequency coupling (CFC) reflects the coordinated effect between different frequency components (e.g., theta and gamma) of local field potentials (LFPs) during WM. In this study, we try to map the changes that occur in the brain networks during WM at the level of CFC between theta-gamma of LFPs. First, a 16-channel brain network by using the CFC between theta-gamma of LFPs during WM was constructed. Then, the dynamic properties of the brain network during WM were analyzed based on graph theory. Experimental results show that the LFPs power increased at the WM state than at resting stat, but decreased across learning; the CFC between theta-gamma increased with learning days and phase-amplitude coupling (PAC) in the WM state was higher than that in free choice state and rest state; the changes of average degree, average shortest path length and global efficiency had significant difference on learning days. We can indicate that the CFC between theta-gamma in the network plays an important role in the WM formation. Furthermore, correct storage of WM information will not change local information transmission and the small-world attribute, while, it can increase the network connection and efficiency of information transmission.

Inferring the direction of rhythmic neural transmission via inter-regional phase-amplitude coupling (ir-PAC)

Phase-amplitude coupling (PAC) estimates the statistical dependence between the phase of a low-frequency component and the amplitude of a high-frequency component of local field potentials (LFP). To date PAC has been mainly applied to one signal. In this work, we introduce a new application of PAC to two LFPs and suggest that it can be used to infer the direction and strength of rhythmic neural transmission between distinct brain networks. This hypothesis is based on the accumulating evidence that transmembrane currents related to action potentials contribute a broad-band component to LFP in the high-gamma band, and PAC calculated between the amplitude of high-gamma (>60 Hz) in one LFP and the phase of a low-frequency oscillation (e.g., theta) in another would therefore relate the output (spiking) of one area to the input (somatic/dendritic postsynaptic potentials) of the other. We tested the hypothesis on theta-band long range communications between hippocampus and prefrontal cortex (PFC) and theta-band short range communications between dentate gyrus (DG) and the Ammon’s horn (CA1) within the hippocampus. The ground truth was provided by the known anatomical connections predicting hippocampus → PFC and DG → CA1, i.e., theta transmission is unidirectional in both cases: from hippocampus to PFC and from DG to CA1 along the tri-synaptic pathway within hippocampus. We found that (1) hippocampal high-gamma amplitude was significantly coupled to PFC theta phase, but not vice versa; (2) similarly, DG high-gamma amplitude was significantly coupled to CA1 theta phase, but not vice versa, and (3) the DG high-gamma-CA1 theta PAC was significantly correlated with DG → CA1 Granger causality, a well-established analytical measure of directional neural transmission. These results support the hypothesis that inter-regional PAC (ir-PAC) can be used to relate the output of a rhythmic “driver” network (i.e., high gamma) to the input of a rhythmic “receiver” network (i.e., theta) and thereby establish the direction and strength of rhythmic neural transmission.

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

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

Scale-Free Neural and Physiological Dynamics in Naturalistic Stimuli Processing.

Neural activity recorded at multiple spatiotemporal scales is dominated by arrhythmic fluctuations without a characteristic temporal periodicity. Such activity often exhibits a 1/f-type power spectrum, in which power falls off with increasing frequency following a power-law function: , which is indicative of scale-free dynamics. Two extensively studied forms of scale-free neural dynamics in the human brain are slow cortical potentials (SCPs)—the low-frequency (<5 Hz) component of brain field potentials—and the amplitude fluctuations of α oscillations, both of which have been shown to carry important functional roles. In addition, scale-free dynamics characterize normal human physiology such as heartbeat dynamics. However, the exact relationships among these scale-free neural and physiological dynamics remain unclear. We recorded simultaneous magnetoencephalography and electrocardiography in healthy subjects in the resting state and while performing a discrimination task on scale-free dynamical auditory stimuli that followed different scale-free statistics. We observed that long-range temporal correlation (captured by the power-law exponent β) in SCPs positively correlated with that of heartbeat dynamics across time within an individual and negatively correlated with that of α-amplitude fluctuations across individuals. In addition, across individuals, long-range temporal correlation of both SCP and α-oscillation amplitude predicted subjects’ discrimination performance in the auditory task, albeit through antagonistic relationships. These findings reveal interrelations among different scale-free neural and physiological dynamics and initial evidence for the involvement of scale-free neural dynamics in the processing of natural stimuli, which often exhibit scale-free dynamics.

Cell-type-specific resonances shape the responses of striatal neurons to synaptic input.

Neurons respond to synaptic inputs in cell-type-specific ways. Each neuron type may thus respond uniquely to shared patterns of synaptic input. We applied statistically identical barrages of artificial synaptic inputs to four striatal cell types to assess differences in their responses to a realistic input pattern. Each interneuron type fired in phase with a specific input-frequency component. The fast-spiking interneuron fired in relation to the gamma-band (and higher) frequencies, the low-threshold spike interneuron to the beta-band frequencies, and the cholinergic neurons to the delta-band frequencies. Low-threshold spiking and cholinergic interneurons showed input impedance resonances at frequencies matching their spiking resonances. Fast-spiking interneurons showed resonance of input impedance but at lower than gamma frequencies. The spiny projection neuron's frequency preference did not have a fixed frequency but instead tracked its own firing rate. Spiny cells showed no input impedance resonance. Striatal interneurons are each tuned to a specific frequency band corresponding to the major frequency components of local field potentials. Their influence in the circuit may fluctuate along with the contribution of that frequency band to the input. In contrast, spiny neurons may tune to any of the frequency bands by a change in firing rate.

Generation of field potentials and modulation of their dynamics through volume integration of cortical activity.

Field potentials (FPs) recorded within the brain, often called "local field potentials" (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an "LFP" signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs.

Excitatory and inhibitory contributions to local field potentials in human and monkey

Local field potentials (LFPs) are a common measure of the neuronal population activity. However, their origins are not yet fully understood. A recent in vitro study has shown that even single spikes emitted by an interneuron can trigger detectable unitary field potentials in extracellular medium [1]. Their contributions can be additionally amplified due to strong spatial correlations in interneuronal firing [2]. Nevertheless, inhibitory activity in vivo is strongly correlated with the excitatory potentials leading to effective cancellations of generated field potentials. As a result, the unitary field potentials induced by interneuronal spikes can not be separated from background activity. Here, we describe a technique that allows to disambiguate the excitatory and inhibitory contributions. We study the contribution of excitatory and inhibitory neurons in awake and sleeping brain of human and monkey. The experimental data were recorded intracortically in patients accepted for the surgical treatment of epileptic foci. We discriminated 82 single units over a electrode grid of 92 electrodes (covering an area of 4 mm × 4 mm) together with accompanying local field potentials. We compared the results with LPFs and spikes recorded from electrode arrays of the same geometry implanted in motor cortex of macaque monkeys [3]. For both datasets, we determined the field potential components related to spikes of inhibitory neurons by means of spike-triggered average (STA) and covariance (STC) methods [4]. First, we determined the spatial reach of the spike-induced field by means of spike-triggered average analysis. We found that the potentials triggered by putative interneurons propagate across the electrode grid at velocity higher than the field of putative pyramidal neurons (propagation velocity: 0.5 m/s and 0.3 m/s, respectively). In addition, the spike-triggered covariance analysis revealed gamma-band components in the local field potentials of interneurons but not pyramidal neurons. These high-frequency components are most likely related to the oscillations generated within a local network. To test this hypothesis, we simulate a network of simplified neurons that manifest gamma-band synchronization. Next, we apply the spike-triggered analysis to the field potentials calculated as a local average of the membrane potentials. The results of the simulations are compared to the experimental data. We demonstrate that spike triggered covariance allows to separate components that are not accessible to standard techniques due to cancellations of the field produced by inhibitory and excitatory potentials. The application of this technique to the activities recorded in interneurons revealed previously unidentified components of local field potentials. Computer simulations suggest that these components are related to nonlinear interactions within the networks of inhibitory and excitatory neurons. Interestingly, we have not found such gamma-band components in the LFPs associated with excitatory neurons. Overall, our results point to essentially different relations between LFPs and spikes of excitatory and inhibitory neurons. We propose that this difference may provide a new electrophysiological criterion for the identification of interneurons.

Imidazoleacetic acid-ribotide in the rodent striatum: A putative neurochemical link between motor and autonomic deficits in parkinson’s disease

We have previously demonstrated that imidazole-4-acetic acid-ribotide (IAA-RP) is present in the mammalian brain and is an endogenous ligand at imidazoline binding sites. In the present study, we used a polyclonal antiserum to visualize IAA-RP-containing neurons in the rat caudoputamen. We observe IAA-RP-immunostained neurons scattered throughout the dorsal and ventral striatum. Most of these cells co-localize GABA, but none are parvalbumin-immunoreactive. In contrast, approximately 50% of the calbindin D28k-immunopositive striatal neurons co-localize IAA-RP. Electrophysiological studies using corticostriatal slices demonstrated that bath application of IAA-RP reversibly depresses the synaptically mediated component of field potentials recorded in the striatum by stimulation of cortical axons. Addition of competitive glutamate receptor antagonists completely blocks the response, confirming its association with glutamatergic transmission. Using paired-pulse stimuli, IAA-RP was shown to exert, at least in part, a presynaptic effect, but blockade of GABAA receptor-mediated transmission did not alter the response. Lastly, we show that this effect is attributable to imidazoline-1 receptors, and not to α2 adrenergic receptors. Since IAA-RP is an endogenous central regulator of blood pressure, and cardiovascular dysfunction is a common symptom associated with Parkinson's disease (PD), we speculate that IAA-RP-related abnormalities may underlie some of the autonomic dysfunction that occurs in PD.

Effects of morphine and methadone treatments on glutamatergic transmission in rat frontal cortex

The effects of repeated administration of morphine and methadone, followed by a challenge dose of either morphine or methadone were examined ex vivo in rat frontal cortical slices that were prepared 1h after final drug administration. Morphine challenge dose (5mg/kg), administered 14 days after the end of repeated morphine pretreatment (10mg/kg, administered 7 times) decreased both the AMPA/kainate and the NMDA components of field potentials that were evoked in cortical layer II/III by electrical stimulation. This effect did not occur either when a methadone challenge dose (2.5mg/kg) was administered instead of morphine or after repeated morphine treatment. Moreover, after repeated methadone treatment (2.5mg/kg, administered 7 times), neither morphine nor methadone challenge affected AMPA/kainate or NMDA components of the field potentials. These data indicate a specific effect of repeated morphine followed by morphine challenge on cortical glutamatergic transmission.

Age-Dependent Decline in Supragranular Long-Term Synaptic Plasticity by Increased Inhibition During the Critical Period in the Rat Primary Visual Cortex

Supragranular long-term potentiation (LTP) and depression (LTD) are continuously induced in the pathway from layer 4 during the critical period in the rodent primary visual cortex, which limits the use of supragranular long-term synaptic plasticity as a synaptic model for the mechanism of ocular dominance (OD) plasticity. The results of the present study demonstrate that the pulse duration of extracellular stimulation to evoke a field potential (FP) is critical to induction of LTP and LTD in this pathway. LTP and LTD were induced in the pathway from layer 4 to layer 2/3 in slices from 3-wk-old rats when FPs were evoked by 0.1- and 0.2-ms pulses. LTP and LTD were induced in slices from 5-wk-old rats when evoked by stimulation with a 0.2-ms pulse but not by stimulation with a 0.1-ms pulse. Both the inhibitory component of FP and the inhibitory/excitatory postsynaptic potential amplitude ratio evoked by stimulation with a 0.1-ms pulse were greater than the values elicited by a 0.2-ms pulse. Stimulation with a 0.1-ms pulse at various intensities that showed the similar inhibitory FP component with the 0.2-ms pulse induced both LTD and LTP in 5-wk-old rats. Thus extracellular stimulation with shorter-duration pulses at higher intensity resulted in greater inhibition than that observed with longer-duration pulses at low intensity. This increased inhibition might be involved in the age-dependent decline of synaptic plasticity during the critical period. These results provide an alternative synaptic model for the mechanism of OD plasticity.

Transcranial photo-inactivation of neural activities in the mouse auditory cortex

Flavoprotein fluorescence in the brain is intimately coupled with neuronal aerobic energy metabolism. If flavoproteins are photobleached, neural activities may be affected owing to dysfunction in aerobic energy metabolism in mitochondria. We tested this possibility in cortical slices from mice, and found that exposure to blue light ( λ = 475 nm) derived from a 20 mW diode laser for 50 min suppresses trans-synaptic components of field potentials. This finding formed the basis of a transcranial photo-inactivation technique, that was used to investigate auditory signal transmission between the anterior auditory field (AAF) and the primary auditory cortex (AI) in anesthetized mice. Cortical responses in AAF and AI, elicited by 5 kHz tonal stimuli, were visualized using transcranial flavoprotein fluorescence imaging. After determining responsive areas in AAF and AI, the auditory cortex was exposed to the blue diode laser via the intact skull, while either AAF or AI was protected with a piece of carbon paper. Although the photo-inactivation of AI had no significant effect on the fluorescence responses in AAF, the photo-inactivation of AAF significantly reduced the fluorescence responses in AI, indicating the presence of auditory signal transmission from AAF to AI.

Long-term depression induced by local tetanic stimulation in the rat auditory cortex

In sensory cortices, synaptic plasticities such as long-term potentiation (LTP) and long-term depression (LTD) have important roles in the development of neural circuits and sensory information processing. However, the differential roles and mechanisms of the various types of LTP and LTD are not clear. In the present study, we investigated LTP and two types of LTD in slices obtained from the rat auditory cortex. Supragranular field potentials elicited by layer VI stimulation were recorded through a metal electrode. Transsynaptic field potentials exhibited marked LTP after tetanic stimulation (TS, 100 Hz for 1 s) was applied to layer VI. The same field potential components exhibited LTD after low-frequency stimulation (LFS, 1 Hz for 900 s) was applied to layer VI. LTD of supragranular field potentials was also induced by local TS applied to supragranular layers 0.3 mm from the recording site. Neither LTP nor LTD of either type was induced in the presence of 50 μM d-(−)-2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist. However, 500 μM (+)-α-methyl-4-carboxyphenylglycine (MCPG), an antagonist of metabotropic glutamate receptors, had no effect. LTD induced by LFS and that induced by local TS were suppressed in the presence of 3 μM bicuculline, an antagonist of GABA A receptors. Each of these forms of LTD occluded the other. These results and intracellular recordings in supragranular pyramidal neurons during LFS and local TS strongly suggest that the two types of LTD share common neural circuits for their induction.

Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization

The electrophysiological properties of acute and chronic methylphenidate (MPD) on neurons of the prefrontal cortex (PFC) and caudate nucleus (CN) have not been studied in awake, freely behaving animals. The present study was designed to investigate the dose–response effects of MPD on sensory evoked potentials recorded from the PFC and CN in freely behaving rats previously implanted with permanent electrodes, as well as their behavioral (locomotor) activities. On experimental day 1, locomotor behavior of rats was recorded for 2 h post-saline injection, and sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10 mg/kg, i.p., MPD administration. Animals were injected for the next five days with daily 2.5 mg/kg MPD to elicit behavioral sensitization. Locomotor recording was resumed on experimental days 2 and 6 after the MPD maintenance dose followed by 3 days of washout. On experimental day 10, rats were connected again to the electrophysiological recording system and rechallenged with saline and the identical MPD doses as on experimental day 1. On experimental day 11, rat's locomotor recording was resumed before and after 2.5 mg/kg MPD administration. Behavioral results showed that repeated administration of MPD induced behavioral sensitization. Challenge doses (0.6, 2.5, and 10.0 mg/kg) of MPD on experimental day 1 elicited dose–response attenuation in the response amplitude of the average sensory evoked field potential components recorded from the PFC and CN. Chronic MPD administration resulted in attenuation of the PFC's baseline recorded on experimental day 10, while the same treatment did not modulate the baseline recorded from the CN. Treatment of MPD on experimental day 10 resulted in further decrease of the average sensory evoked response compared to that obtained on experimental day 1. This observation of further decrease in the electrophysiological responses after chronic administration of MPD suggests that the sensory evoked responses on experimental day 10 represent neurophysiological sensitization. Moreover, two different response patterns were obtained from PFC and CN following chronic methylphenidate administration. In PFC, the baseline and effect of methylphenidate expressed electrophysiological sensitization on experimental day 10, while recording from CN did not exhibit any electrophysiological sensitization.

Long-term depression in the sensorimotor cortex induced by repeated delivery of 10 Hz trains in vivo

Memory consolidation in the neocortex is thought to be mediated in part by bi-directional modifications of synaptic strength. The sensorimotor cortex shows marked spontaneous activity near 10 Hz during both waking and sleep in the form of electroencephalographic spindle waves, and is also sensitive to electrical activation of inputs at 10 Hz. Induction of long-term synaptic depression in corpus callosum inputs to layer V of the sensorimotor cortex of the awake, adult rat requires repeated low-frequency stimulation over many days. To determine if 10 Hz stimulation may facilitate the induction of long-term depression, we compared the amounts of long-term depression induced by conventional 1 Hz trains, repeated delivery of 450 pairs of stimulation pulses using a 100 ms interpulse interval, and 45 short, 2 s, 10 Hz trains. Each pattern was delivered daily for 10 days and was matched for total duration and number of pulses. Changes in synaptic responses were assessed by monitoring field potentials evoked by stimulation of the corpus callosum. A facilitation of synaptic responses in layer V was observed during delivery of both paired-pulse trains and 10 Hz trains. There was no significant difference in long-term depression induced by 1 Hz stimulation and repeated paired-pulse stimulation, but 10 Hz trains induced significantly greater long-term depression than 1 Hz trains in both the early monosynaptic and late polysynaptic field potential components. The effectiveness of short 10 Hz trains for the induction of long-term depression suggests that synchronous population activity at frequencies near 10 Hz such as spindle waves may contribute to endogenous synaptic depression in sensorimotor cortex.