Local Field Potential Amplitude Research Articles

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Introduction: Millions of children and young adults are living with disabilities from traumatic brain injury (TBI) in childhood. Very little is known about age-dependent pathways of neuroplasticity on post-injury recovery. Hypothesis: We hypothesized that we could detect deficits in neuronal activity after TBI in the immature rat using electrophysiology recordings and functional magnetic resonance imaging (fMRI). Methods: Rats (P 16-18, n=10) underwent controlled cortical impact (CCI) to the left parietal cortex. Control rats (n=10) were age-matched, uninjured pups. Two weeks after CCI, the functional response of the uninjured (right) primary somatosensory cortex (S1) was measured with electrophysiology recording in response to left forepaw stimulation. Multi-unit activities (MUA) and local field potentials (LFP) were recorded with a 12-channel axial array electrode. The number of neuronal spiking events was calculated by post stimulus time histogram (PSTH) analysis of MUA. Rats also underwent blood oxygenation level dependent (BOLD) fMRI. Neuronal connections in the thalamo-cortical and cortical-cortical somatosensory pathways were evaluated by using manganese enhanced magnetic resonance imaging (MEMRI) and histology. Results: Electrophysiology recordings showed decreases in spiking rates across laminae II-V in the uninjured S1 of TBI rats (p<0.05). Stimulation on the left forepaw in TBI rats resulted in decreased LFP amplitude (laminae II-V) and increased LFP latency (laminae IV-V) in the uninjured S1 (p<0.05). Left forepaw stimulation also evoked decreases in the extent of fMRI responses in the uninjured S1 in TBI rats. MEMRI imaging did not show changes in the thalamo-cortical connections in the uninjured S1. However, luxo-blue staining showed decreases in the axon myelination volume along the corpus callosum connecting cortical-cortical somatosensory pathways (p<0.05, TBI vs controls). Conclusions: We conclude that TBI in immature rats adversely affects neuronal function of the contralateral (uninjured) S1 cortex, in part due to alterations in the cortical-cortical somatosensory pathways. These findings have implications for understanding recovery after pediatric TBI. Support: Johns Hopkins Brain Science Institute

The Laminar Cortex Model: A New Continuum Cortex Model Incorporating Laminar Architecture

Local field potentials (LFPs) are widely used to study the function of local networks in the brain. They are also closely correlated with the blood-oxygen-level-dependent signal, the predominant contrast mechanism in functional magnetic resonance imaging. We developed a new laminar cortex model (LCM) to simulate the amplitude and frequency of LFPs. Our model combines the laminar architecture of the cerebral cortex and multiple continuum models to simulate the collective activity of cortical neurons. The five cortical layers (layer I, II/III, IV, V, and VI) are simulated as separate continuum models between which there are synaptic connections. The LCM was used to simulate the dynamics of the visual cortex under different conditions of visual stimulation. LFPs are reported for two kinds of visual stimulation: general visual stimulation and intermittent light stimulation. The power spectra of LFPs were calculated and compared with existing empirical data. The LCM was able to produce spontaneous LFPs exhibiting frequency-inverse (1/ƒ) power spectrum behaviour. Laminar profiles of current source density showed similarities to experimental data. General stimulation enhanced the oscillation of LFPs corresponding to gamma frequencies. During simulated intermittent light stimulation, the LCM captured the fundamental as well as high order harmonics as previously reported. The power spectrum expected with a reduction in layer IV neurons, often observed with focal cortical dysplasias associated with epilepsy was also simulated.

Long-term Recordings of Local Field Potentials From Implanted Deep Brain Stimulation Electrodes

Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for Parkinson disease. However, DBS is not responsive to an individual's disease state, and programming parameters, once established, do not change to reflect disease state. Local field potentials (LFPs) recorded from DBS electrodes are being investigated as potential biomarkers for the Parkinson disease state. However, no patient data exist about what happens to LFPs over the lifetime of the implant. We investigated whether LFP amplitude and response to limb movement differed between patients implanted acutely with subthalamic nucleus DBS electrodes and patients implanted 2 to 7 years previously. We recorded LFPs at DBS surgery time (9 subjects), 3 weeks after initial placement (9 subjects), and 2 to 7 years (median: 3.5) later during implanted programmable generator replacement (11 sides). LFP power-frequency spectra for each of 3 bipolar electrode derivations of adjacent contacts were calculated over 5-minute resting and 30-second movement epochs. Monopolar impedance data were used to evaluate trends over time. There was no significant difference in β-band LFP amplitude between initial electrode implantation (OR) and 3-week post-OR times (P=.94). However, β-band amplitude was lower at implanted programmable generator replacement times than in OR (P=.008) and post-OR recordings (P=.039). Impedance measurements declined over time (P<.001). Postoperative LFP activity can be recorded years after DBS implantation and demonstrates a similar profile in response to movement as during acute recordings, although amplitude may decrease. These results support the feasibility of constructing a closed-loop, patient-responsive DBS device based on LFP activity.

Protective Effects of the CB1 Receptor Agonist WIN 55.212-2 during Development of Seizure Activity in the Brain in Models of Temporal Epilepsy in Vivo

The effects of intracerebral intraventricular administration of the nonselective cannabinoid CB1 receptor WIN 55.212-2 (1 μM, 2 μl) on seizure activity were studied in conscious guinea pigs. Changes in local field potential and convulsive discharges evoked by electrical stimulation of the perforant path were recorded simultaneously in the hippocampus, entorhinal cortex, medial septal area, and amygdala after prior administration of WIN 55.212-2 or the organic solvent DMSO. In 80% of tests, WIN 55.212-2 was found to block the development of seizure activity. Repeated injections of agonist for 30 days increased the amplitude of local field potentials and the power of the theta rhythm in all structures recorded. Administration of kainic acid provoked status epilepticus in control animals, while status epilepticus did not arise in guinea pigs given daily agonist injections for 25–30 days. The possible mechanisms of the protective effects of WIN 55.212-2 are discussed.

Beta band stability over time correlates with Parkinsonian rigidity and bradykinesia

Abnormal oscillatory activity in the basal ganglia is increasingly implicated in the pathophysiology of Parkinson's disease. Such activity is recorded in patients in the form of oscillations in the local field potential (LFP) picked up in the subthalamic nucleus. Previous studies have focused on correlations between features of the time averaged power or amplitude spectrum of the LFP and the clinical state, either off medication or in response to levodopa. However, average spectral densities do not take account of time variant spectral properties and we hypothesised that these dynamic properties of the spectrum of the LFP would contain additional information about clinical state. Here we assess the variability in LFP amplitude over time using the coefficient of variation (CV), evaluating this with regard to clinical state off medication and in response to levodopa in two datasets. The CV of activity in the high beta frequency band was found to be correlated with clinical state off levodopa (rho=−0.59, p<0.001) and this was shown to be complementary, rather than redundant, to spectral amplitude in a multiple regression analysis, selective for rigidity–bradykinesia and highly focal. Similarly, a strong correlation was found between change in clinical scores and change in high beta CV following levodopa (rho=−0.66, p=0.004). This too was selective for rigidity–bradykinesia and non-redundant to spectral power in a multiple regression model. Our results indicate that temporal stability in the beta band is correlated with rigidity–bradykinesia. It is suggested that loss of beta reactivity is deleterious to basal ganglia function over and above any concomitant change in absolute level of beta synchrony. The CV of LFP beta band amplitude may potentially provide an additional index of clinical state suitable for feedback control in closed loop stimulation therapy.

An Automated Classification Method for Single Sweep Local Field Potentials Recorded from Rat Barrel Cortex under Mechanical Whisker Stimulation

Understanding brain signals as an outcome of brain’s information processing is a challenge for the neuroscience and neuroengineering community. Rodents sense and explore the environment through whisking. The local field potentials (LFPs) recorded from the barrel 28 columns of the rat somatosensory cortex (S1) during whisking provide information about the tactile information processing pathway. Particularly when using large-scale high-resolution neuronal probes, during each experiment many single LFPs are recorded as an outcome of underlying neuronal network activation and averaged to extract information. However, single LFP signals are frequently very different from each other and extracting information provided by their shape is a useful way to better decode information transmitted by the network. In this work, we propose an automated method capable of classifying these signals based on their shapes. We used template matching approach to recognize single LFPs and extracted the contour information from the recognized signal to generate a feature matrix, which is then classified using the intelligent K–means clustering. As an application example, shape specific information (e.g., latency, and amplitude) of LFPs evoked in the rat somatosensory barrel cortex and used in decoding the rat whiskers information processing pathway is provided by the method.

Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator

In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methods for chronic recording are limited. Here we present a technique for long-term investigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals report sensory-evoked activity in anaesthetized mouse somatosensory cortex with high sensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations.

Close temporal coupling of neuronal activity and tissue oxygen responses in rodent whisker barrel cortex

Neuronal activity elicits metabolic and vascular responses, during which oxygen is first consumed and then supplied to the tissue via an increase in cerebral blood flow. Understanding the spatial and temporal dynamics of blood and tissue oxygen () responses following neuronal activity is crucial for understanding the physiological basis of functional neuroimaging signals. However, our knowledge is limited because previous measurements have been made at low temporal resolution (>100 ms). Here we recorded at high temporal resolution (1 ms), simultaneously with co-localized field potentials, at several cortical depths from the whisker region of the somatosensory cortex in anaesthetized rats and mice. Stimulation of the whiskers produced rapid, laminar-specific changes in . Positive responses (i.e. increases) were observed in the superficial layers within 50 ms of stimulus onset, faster than previously reported. Negative responses (i.e. decreases) were observed in the deeper layers, with maximal amplitude in layer IV, within 40 ms of stimulus onset. The amplitude of the negative, but not the positive, response correlated with local field potential amplitude. Disruption of neurovascular coupling, via nitric oxide synthase inhibition, abolished positive responses to whisker stimulation in the superficial layers and increased negative responses in all layers. Our data show that responses occur rapidly following neuronal activity and are laminar dependent.

Spatiotemporal Variation of Multiple Neurophysiological Signals in the Primary Motor Cortex during Dexterous Reach-to-Grasp Movements

To examine the spatiotemporal distribution of discriminable information about reach-to-grasp movements in the primary motor cortex upper extremity representation, we implanted four microelectrode arrays in the anterior bank and lip of the central sulcus in each of two monkeys. We used linear discriminant analysis to compare information, quantified as decoding accuracy, contained in various neurophysiological signals. For all signal types, decoding accuracy increased immediately after the movement cue, peaked around movement onset, and declined during the static hold. Spike recordings and local field potential (LFP) time domain amplitude provided more discriminable information than LFP frequency domain power. Discriminable information on movement type was distributed evenly across recording sites by LFP amplitude and 1-4 Hz power but unevenly by 100-170 Hz power and spike recordings. These latter two signal types provided higher decoding accuracies closer to the hemispheric surface than deep in the anterior bank and also provided accuracies that varied along the central sulcus. This variation in the distribution of movement-type information may be related to differences in the rostral versus caudal regions of the primary motor cortex and to its underlying somatotopic organization. The even distribution of information by LFP amplitude and 1-4 Hz power compared with the more localized distribution by 100-170 Hz power and spikes suggest that these different neurophysiological signals reflect different underlying processes that distribute information through the motor cortex during reach-to-grasp movements.

How local is the local field potential?

The local field potential (LFP), usually referring to the low-frequency part of an extracellularly recorded potential (< 500 Hz), is nowadays routinely measured together with the spiking activity. The LFP is commonly believed to mainly reflect synaptic activity in a local population surrounding the electrode [1] but how large this population is, i.e. how many neurons contribute to the signal, is still debated. In this modeling study we investigate which factors influence the spatial summation of contributions that generate the LFP signal. A better understanding of this is crucial for a correct interpretation of the LFP, especially when analyzing multiple LFP signals recorded simultaneously at different cortical sites. We use a simplified two-dimensional model of a cortical population of neurons where the LFP is constructed as a weighted sum of signal contributions from all cells within a certain radial distance to the recording electrode. First we consider a general formulation of the model: if the single-cell LFP contributions can be viewed as current dipole sources [2], the single-cell amplitude will decay as 1/r2 with distance r to the electrode. On the other hand, for the two-dimensional geometry considered here, the number of neurons at a given distance increases linearly with r. In addition to these two opposed scaling factors the amplitude of the summed LFP signal also depends on how correlated the single-cell LFP sources are. We calculate the LFP amplitude as a function of the population radius and relate it to the above factors. We show that if the single-cell contributions decay as dipole sources or more steeply with distance, and if the sources are uncorrelated, the LFP is originating from a small local population. Cells outside of this population do not contribute to the LFP. If, however, the different LFP sources are uniformly correlated, cells at any distance contribute substantially to the LFP amplitude. In this case the LFP reach is only limited by the size of the region of correlated sources. This result highlights that the spatial region of the LFP is not fixed; rather it changes with the dynamics of the underlying synaptic activity. We further validate these results through LFP simulations of morphologically reconstructed cortical cells [2-4] where we study the effects of neuronal morphology on the size of the region contributing to the LFP. Finally, we show the laminar dependence of the reach measure used here and discuss potential implications of the interpretation of experimentally recorded LFPs.

The Local Field Potential Reflects Surplus Spike Synchrony

While oscillations of the local field potential (LFP) are commonly attributed to the synchronization of neuronal firing rate on the same time scale, their relationship to coincident spiking in the millisecond range is unknown. Here, we present experimental evidence to reconcile the notions of synchrony at the level of spiking and at the mesoscopic scale. We demonstrate that only in time intervals of significant spike synchrony that cannot be explained on the basis of firing rates, coincident spikes are better phase locked to the LFP than predicted by the locking of the individual spikes. This effect is enhanced in periods of large LFP amplitudes. A quantitative model explains the LFP dynamics by the orchestrated spiking activity in neuronal groups that contribute the observed surplus synchrony. From the correlation analysis, we infer that neurons participate in different constellations but contribute only a fraction of their spikes to temporally precise spike configurations. This finding provides direct evidence for the hypothesized relation that precise spike synchrony constitutes a major temporally and spatially organized component of the LFP.

Disrupted Activity in the Hippocampal–Accumbens Circuit of Type III Neuregulin 1 Mutant Mice

Neuregulin 1 (Nrg1), a schizophrenia susceptibility gene, is involved in fundamental aspects of neurodevelopment. Mice lacking any one of the several isoforms of Nrg1 have a variety of schizophrenia-related phenotypes, including deficits in working memory and sensorimotor gating, loss of spines in pyramidal neurons in the ventral subiculum, loss of dendrites in cortical pyramidal cells, loss of parvalbumin-positive interneurons in the prefrontal cortex, and altered plasticity in corticolimbic synapses. Mice heterozygous for a disruption in exon 7 of the Nrg1 gene lack Type III (cysteine-rich-domain-containing) isoforms and have sensorimotor gating deficits that may involve changes in the activity of a circuit involving projections from the ventral hippocampus (vHPC) to medium spiny neurons in the nucleus accumbens (nACC). To explore the neural basis of these deficits, we examined electrophysiological activity in the nACC and vHPC of these mice. Under urethane anesthesia, bursts of spontaneous activity propagated from the vHPC to the nACC in both wild-type and mutant mice. However, these bursts were weaker in mutant nACC, with reduced local field potential amplitude and spiking activity. Single units in mutant nACC fired less frequently within the bursts, and more frequently outside of the bursts. Moreover, within-burst nACC spiking was less modulated by vHPC activity, as determined by phase-locking to the low-frequency oscillatory components of the bursts. These data suggest that the efficacy of vHPC input to the nACC is reduced in the Type III Nrg1 heterozygotes, supporting a role for Nrg1 in the functional profile of hippocampal-accumbens synapses.

Fast Propagating Waves within the Rodent Auditory Cortex

Central processing of acoustic signals is assumed to take place in a stereotypical spatial and temporal pattern involving different fields of auditory cortex. So far, cortical propagating waves representing such patterns have mainly been demonstrated by optical imaging, repeatedly in the visual and somatosensory cortex. In this study, the surface of rat auditory cortex was mapped by recording local field potentials (LFPs) in response to a broadband acoustic stimulus. From the peak amplitudes of LFPs, cortical activation maps were constructed over 4 cortical auditory fields. Whereas response onset had same latencies across primary auditory field (A1), anterior auditory field (AAF), and ventral auditory field and longer latencies in posterior auditory field, activation maps revealed a reproducible wavelike pattern of activity propagating for ∼45 ms poststimulus through all cortical fields. The movement observed started with 2 waves within the primary auditory fields A1 and AAF moving from ventral to dorsal followed by a motion from rostral to caudal, passing continuously through higher-order fields. The pattern of propagating waves was well reproducible and showed only minor changes if different anesthetics were used. The results question the classical "hierarchical" model of cortical areas and demonstrate that the different fields process incoming information as a functional unit.

Cell‐specific contribution to gamma oscillations

Gamma oscillations are a particularly prominent form of rhythmic activity occurring during wakefulness and attentive behaviour that result from synchronous activity of cortical neurons at frequencies ranging between 20 and 80 Hz. Abnormalities in these oscillations might underlie neuropsychiatric disorders such as schizophrenia (Uhlhaas et al. 2006). Therefore understanding the precise mechanisms underlying gamma oscillations – in particular the respective role of synaptic and intrinsic currents – represents a major goal in fundamental and clinical neuroscience. Gamma oscillations are prevalent in the hippocampus in vivo and they can be induced in the isolated CA3 region of the hippocampus in vitro with bath application of carbachol (Fisahn et al. 1998). They require both excitatory and inhibitory synaptic transmission. In particular, in their pioneering study Fisahn and co-workers highlighted the role of GABAergic activity by showing that prolongation of the GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) with barbiturate reduced the frequency of gamma oscillations. Models of leaky integrate-and-fire neurons suggest that synaptic recurrent feedback loops between interneurons and pyramidal cells are necessary and sufficient to explain gamma frequency oscillations (Brunel & Wang, 2003). In a recent study, gamma oscillation fluctuations in amplitude and frequency were found to be correlated with cycle-to-cycle changes in excitation and inhibition (Atallah & Scanziani, 2009). In this issue of The Journal of Physiology, Oren, Hájos and Paulsen (Oren et al. (2010) examined the relative contribution of synaptic and voltage-dependent action currents in pyramidal neurons during gamma oscillations induced with carbachol in the CA3 region of the rat hippocampus in vitro. They combined recordings of the local field potential (LFP) to monitor the oscillatory activity of the principal neurons with cell-attached recordings from subclasses of GABAergic interneurons. Changes in the oscillation amplitude were quantified by the amplitude of the wavelet transform. Oren et al. confirm in this study that inhibitory currents contribute significantly to LFP amplitude fluctuations as a consequence of an increased probability of firing in subclasses of interneurons that are responsible for perisomatic inhibition. Indeed when performing cell-attached recordings from various cell types, the authors could observe that, for a given oscillation cycle, the mean cycle amplitude was significantly higher when perisomatic (or interneuron-selective) interneurons discharged. In contrast, there was no such direct relationship between the discharge of a pyramidal cell and LFP amplitude. Therefore cycle-to-cycle variation amplitude appears to be the direct consequence of interneuron firing probability. However, the synchronized firing of pyramidal cells, which can be detected as a population spike in some cycles during gamma waves, affected the LFP. Indeed, the authors provide evidence that slow action currents, resulting from the activation of repolarisation conductances contribute in a significant manner to the early component of the LFP. Local field potentials are probably one of the oldest, least invasive and simplest ways to perform high sampling rate recordings of not only neuronal assemblies, but also the discharge activity of single neurons with the help of combined on- and offline signal processing analysis. The possibility of performing high rate recordings with almost no recording time limitation can then become an advantage in comparison with imaging techniques. Oren, Hájos and Paulsen have proven that these techniques should not yet be considered out of date since their use, in combination with other electrophysiological techniques (cell-attached and whole-cell recordings), can be useful and very informative for studying network activity and the contribution of different cell subtypes to the genesis or modulation of cortical oscillations. In this study, the firing probability of dendritic-targeting interneurons was reported not to be correlated with LFP amplitude fluctuations. This in vitro observation is in agreement with in vivo experiments showing that the discharge of these interneurons is not coupled to gamma oscillations (Tukker et al. 2007). Knowing that these interneurons exert specific inhibitory functions on EPSP integration and dendritic electrogenesis but not on action potential firing (Miles et al. 1996) leaves them free to serve distinct functions than the ‘sole’ contribution to gamma oscillations.

Distinct Superficial and deep laminar domains of activity in the visual cortex during rest and stimulation

Spatial patterns of spontaneous neural activity at rest have previously been associated with specific networks in the brain, including those pertaining to the functional architecture of the primary visual cortex (V1). However, despite the prominent anatomical differences between cortical layers, little is known about the laminar pattern of spontaneous activity in V1. We address this topic by investigating the amplitude and coherence of ongoing local field potential (LFP) signals measured from different layers in V1 of macaque monkeys during rest and upon presentation of a visual stimulus. We used a linear microelectrode array to measure LFP signals at multiple, evenly spaced positions throughout the cortical thickness. Analyzing both the mean LFP amplitudes and between-contact LFP coherences, we identified two distinct zones of activity, roughly corresponding to superficial and deep layers, divided by a sharp transition near the bottom of layer 4. The LFP signals within each laminar zone were highly coherent, whereas those between zones were not. This functional compartmentalization was found not only during rest, but also when the receptive field was stimulated during a visual task. These results demonstrate the existence of distinct superficial and deep functional domains of coherent LFP activity in V1 that may reflect the intrinsic interplay of V1 microcircuitry with cortical and subcortical targets, respectively.

Long‐range effects of GABAergic inhibition in gerbil primary auditory cortex

Throughout the literature, the effects of iontophoretically applied neurotransmitter agonists or antagonists on the local activity of neurons are typically studied at the site of drug application. Recently, we have demonstrated long-range inhibitory interactions within the primary auditory cortex (AI) that are effective in complex acoustic situations. To further characterize this long-range functional connectivity, we here report the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the GABA(A) antagonist gabazine (SR 95531) on neuronal activity as a function of distance from the application site reaching beyond the diffusion radius of the applied drug. Neuronal responses to pure tone stimulation were simultaneously recorded at the application site and four additional sites, at distances between 300 and 1350 microm from the application site. We found that whereas application of GABA during best frequency (BF) stimulation in general led to a decrease, and gabazine to an increase, in neuronal activity at the application site, a considerable number of units at remote recording sites showed effects opposite to these local, drug-induced effects. These effects were seen both in spiking activity and in amplitudes of local field potentials. At all locations, the effects varied as a function of pure tone stimulation frequency, pointing to a Mexican-hat-like input function resulting from thalamic inputs to the BF region of the cortical neurons and intracortical interconnections projecting to off-BF regions of the neurons. These data demonstrate the existence of long-range, inhibitory interactions within the gerbil AI, realized either by long-range inhibitory projections or by long-range excitatory projections to local inhibitory interneurons.

Ipsilateral cortical fMRI responses after peripheral nerve damage in rats reflect increased interneuron activity.

In the weeks following unilateral peripheral nerve injury, the deprived primary somatosensory cortex (SI) responds to stimulation of the ipsilateral intact limb as demonstrated by functional magnetic resonance imaging (fMRI) responses. The neuronal basis of these responses was studied by using high-resolution fMRI, in vivo electrophysiological recordings, and juxtacellular neuronal labeling in rats that underwent an excision of the forepaw radial, median, and ulnar nerves. These nerves were exposed but not severed in control rats. Significant bilateral increases of fMRI responses in SI were observed in denervated rats. In the healthy SI of the denervated rats, increases in fMRI responses were concordant with increases in local field potential (LFP) amplitude and an increased incidence of single units responding compared with control rats. In contrast, in the deprived SI, increases in fMRI responses were associated with a minimal change in LFP amplitude but with increased incidence of single units responding. Based on action potential duration, juxtacellular labeling, and immunostaining results, neurons responding to intact forepaw stimulation in the deprived cortex were identified as interneurons. These results suggest that the increases in fMRI responses in the deprived cortex reflect increased interneuron activity.

Dynamics of Evoked Local Field Potentials in the Hippocampus of Epileptic Rats With Spontaneous Seizures

A change in neuronal network excitability within the hippocampus is one of the hallmarks of temporal lobe epilepsy (TLE). In the dentate gyrus (DG), however, neuronal loss and mossy fiber sprouting are associated with enhanced inhibition rather than progressive hyperexcitability. The aim of this study was to investigate how alterations in excitability take place in association with spontaneous seizures expressed in the DG before, during, and after a seizure. For this purpose, we used freely moving rats that had developed spontaneous seizures after a kainate-induced status epilepticus (SE). Continuous EEG was recorded in the DG during several days along with local field potentials (LFPs) that were evoked every 15-30 s by applying paired-pulse stimuli to the angular bundle. Input-output relations showed increased paired pulse depression in epileptic compared with control rats, suggesting a rather strong inhibition in the DG during the interictal state. A characteristic pattern of changes in intrinsic excitability was observed during the ictal period: an increase in the population spike (PS) amplitude, mostly during the early phase of a seizure and often followed by a decrease of the main evoked potential amplitude. The paired-pulse extracellular postsynaptic potential (fEPSP) ratio increased during the seizure and did slowly recover to preictal levels after the seizure ended. Although clear changes in excitability occurred during and after seizure activity, changes of LFP parameters were more subtle before seizure onset; a significant reduction of LFP and PS amplitudes was observed that started 1-2 min in advance in approximately 33% of the cases; in approximately 18%, an increase of LFP/PS amplitude was observed; in the other cases, no significant change was observed. Taken together, these results provide evidence that, in this experimental model, DG physiology is more likely to follow the already ongoing seizure activity rather than to contribute to its generation.

Increasing Spectrotemporal Sound Density Reveals an Octave-Based Organization in Cat Primary Auditory Cortex

Auditory neurons are likely adapted to process complex stimuli, such as vocalizations, which contain spectrotemporal modulations. However, basic properties of auditory neurons are often derived from tone pips presented in isolation, which lack spectrotemporal modulations. In this context, it is unclear how to deduce the functional role of auditory neurons from their tone pip-derived tuning properties. In this study, spectrotemporal receptive fields (STRFs) were obtained from responses to multi-tone stimulus ensembles differing in their average spectrotemporal density (i.e., number of tone pips per second). STRFs for different stimulus densities were derived from multiple single-unit activity (MUA) and local field potentials (LFPs), simultaneously recorded in primary auditory cortex of cats. Consistent with earlier studies, we found that the spectral bandwidth was narrower for MUA compared with LFPs. Both neural firing rate and LFP amplitude were reduced when the density of the stimulus ensemble increased. Surprisingly, we found that increasing the spectrotemporal sound density revealed with increasing clarity an over-representation of response peaks at frequencies of approximately 3, 5, 10, and 20 kHz, in both MUA- and LFP-derived STRFs. Although the decrease in spectral bandwidth and neural activity with increasing stimulus density can likely be accounted for by forward suppression, the mechanisms underlying the over-representation of the octave-spaced response peaks are unclear. Plausibly, the over-representation may be a functional correlate of the periodic pattern of corticocortical connections observed along the tonotopic axis of cat auditory cortex.

Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning

Nicotinic acetylcholine receptors (nAChRs) contribute to sensory-cognitive function, as demonstrated by evidence that nAChR activation enhances, and nAChR blockade impairs, neural processing of sensory stimuli and sensory-cognitive behavior. To better understand the relationship between nAChR function and behavior, here we compare the strength of nAChR-mediated physiology in individual animals to their prior auditory behavioral performance. Adult rats were trained on an auditory-cued, active avoidance task over 4 days and classified as “good,” “intermediate” or “poor” performers based on their initial rate of learning and eventual level of performance. Animals were then anesthetized, and tone-evoked local field potentials (LFPs) recorded in layer 4 of auditory cortex (ACx) before and after a test dose of nicotine (0.7mg/kg, s.c.) or saline. In “good” performers, nicotine enhanced LFP amplitude and decreased response threshold to characteristic frequency (CF) stimuli, yet had opposite effects (decreased amplitude, increased threshold) on responses to spectrally distant stimuli; i.e., cortical receptive fields became more selective for CF stimuli. In contrast, nicotine had little effect on LFP amplitude in “intermediate” or “poor” performing animals. Nicotine did, however, reduce LFP onset latency in all three groups, indicating that all received an effective dose of the drug. Our findings suggest that nicotinic regulation of cortical receptive fields may be a distinguishing feature of the best-performing animals, and may facilitate sensory-related learning by enhancing receptive field selectivity.