Field Potentials In Rats Research Articles

Behaviourally modulated hippocampal theta oscillations in the ferret persist during both locomotion and immobility

Theta oscillations are a hallmark of hippocampal activity across mammals and play a critical role in many hippocampal models of memory and spatial navigation. To reconcile the cross-species differences observed in the presence and properties of theta, we recorded hippocampal local field potentials in rats and ferrets during auditory and visual localisation tasks designed to vary locomotion and sensory attention. Here, we show that theta oscillations occur during locomotion in both ferrets and rats, however during periods of immobility, theta oscillations persist in the ferret, contrasting starkly with the switch to large irregular activity (LIA) in the rat. Theta during immobility in the ferret is identified as analogous to Type 2 theta that has been observed in rodents due to its sensitivity to atropine, and is modulated by behavioural state with the strongest theta observed during reward epochs. These results demonstrate that even under similar behavioural conditions, differences exist between species in the relationship between theta and behavioural state.

Chronic, Multi-Site Recordings Supported by Two Low-Cost, Stationary Probe Designs Optimized to Capture Either Single Unit or Local Field Potential Activity in Behaving Rats.

Rodent models of cognitive behavior have greatly contributed to our understanding of human neuropsychiatric disorders. However, to elucidate the neurobiological underpinnings of such disorders or impairments, animal models are more useful when paired with methods for measuring brain function in awake, behaving animals. Standard tools used for systems-neuroscience level investigations are not optimized for large-scale and high-throughput behavioral battery testing due to various factors including cost, time, poor longevity, and selective targeting limited to measuring only a few brain regions at a time. Here we describe two different “user-friendly” methods for building extracellular electrophysiological probes that can be used to measure either single units or local field potentials in rats performing cognitive tasks. Both probe designs leverage several readily available, yet affordable, commercial products to facilitate ease of production and offer maximum flexibility in terms of brain-target locations that can be scalable (32–64 channels) based on experimental needs. Our approach allows neural activity to be recorded simultaneously with behavior and compared between micro (single unit) and more macro (local field potentials) levels of brain activity in order to gain a better understanding of how local brain regions and their connected networks support cognitive functions in rats. We believe our novel probe designs make collecting electrophysiology data easier and will begin to fill the gap in knowledge between basic and clinical research.

Concordant neurophysiological signatures of cognitive control in humans and rats.

Progress towards understanding neural mechanisms in humans relevant to psychiatric conditions has been hindered by a lack of translationally-relevant cognitive tasks for laboratory animals. Accordingly, there is a critical need to develop parallel neurophysiological assessments of domains of cognition, such as cognitive control, in humans and laboratory animals. To address this, we developed a touchscreen-based cognitive (Eriksen Flanker) task in rats and used its key characteristics to construct a novel human version, with similar testing parameters and endpoints across species. We obtained continuous electroencephalogram (EEG) recordings, including local field potentials in rats, and compared electrophysiological signatures locked to stimulus onset and responses across species. We also assessed whether behavioral or physiological task effects were modulated by modafinil, which enhances aspects of cognitive function in humans. In both species, the task elicited expected flanker interference effects (reduced accuracy) during high-conflict trials. Across homologous neuroanatomical loci, stimulus-locked increases in theta power during high-conflict trials as well as error-related negative potentials were observed. These endpoints were not affected by modafinil in either species. Despite some species-specific patterns, our findings demonstrate the feasibility of a rat Flanker task as well as cross-species behavioral and neurophysiological similarities, which may enable novel insights into the neural correlates of healthy and aberrant behavior and provide mechanistic insights relevant to treatment.

Model-Predicted Balance Between Neural Excitation and Inhibition Was Maintained Despite of Age-Related Decline in Sensory Evoked Local Field Potential in Rat Barrel Cortex.

The balance between neural excitation and inhibition has been shown to be crucial for normal brain function. However, it is unclear whether this balance is maintained through healthy aging. This study investigated the effect of aging on the temporal dynamics of the somatosensory evoked local field potential (LFP) in rats and tested the hypothesis that excitatory and inhibitory post-synaptic activities remain balanced during the aging process. The LFP signal was obtained from the barrel cortex of three different age groups of anesthetized rats (pre-adolescence: 4–6 weeks, young adult: 2–3 months, middle-aged adult: 10–20 months) under whisker pad stimulation. To confirm our previous finding that the initial segment of the evoked LFP was solely associated with excitatory post-synaptic activity, we micro-injected gabazine into the barrel cortex to block inhibition while LFP was collected continuously under the same stimulus condition. As expected, the initial slope of the evoked LFP in the granular layer was unaffected by gabazine injection. We subsequently estimated the excitatory and inhibitory post-synaptic activities through a balanced model of the LFP with delayed inhibition as an explicit constraint, and calculated the amplitude ratio of inhibition to excitation. We found an age-dependent slowing of the temporal dynamics in the somatosensory-evoked post-synaptic activity, as well as a significant age-related decrease in the amplitude of the excitatory component and a decreasing trend in the amplitude of the inhibitory component. Furthermore, the delay of inhibition with respect to excitation was significantly increased with age, but the amplitude ratio was maintained. Our findings suggest that aging reduces the amplitude of neural responses, but the balance between sensory evoked excitatory and inhibitory post-synaptic activities is maintained to support normal brain function during healthy aging. Further whole cell patch clamp experiments will be needed to confirm or refute these findings by measuring sensory evoked synaptic excitatory and inhibitory activities in vivo during the normal aging process.

Communication between the Anterior Cingulate Cortex and Ventral Tegmental Area during a Cost-Benefit Reversal Task

The anterior cingulate cortex (ACC) is implicated in value-based decision making, anticipation, and adaptation; however, how ACC activity modulates these behaviors is unclear. One possibility is via the ACC's connections with the ventral tegmental area (VTA), a dopaminergic region implicated in motivation and feedback processing. We tested this by monitoring ACC and VTA local field potentials in rats performing a cost-benefit reversal task that elicited both value-based and anticipatory choices. Partial directed coherence analyses revealed that elevated 4-Hz ACC-to-VTA signaling accompanied decisions that appeared to be anticipatory. ACC-to-VTA signaling also occurred post-reversal, consistent with it being involved in the initiation of non-default behavior. An analysis of 4-Hz signals in the other direction (VTA-to-ACC) revealed that it was elevated when the rats committed errors and that this signal was followed by behavioral adaptation. Together, these findings suggest that bidirectional communication between the ACC and VTA supports behavioral flexibility.

Anodal transcranial direct current stimulation with monopolar pulses improves limb use after stroke by enhancing inter-hemispheric coherence

Post-stroke neurological deficits, such as sensorimotor impairments, are often permanent and a leading cause of disability. Stroke is also associated with changes in neuronal synchrony among different brain areas. Multiple studies demonstrated that non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), enhances the efficacy of existing rehabilitative therapies. We hypothesized that the therapeutic effects of tDCS could be due to its influence on neuronal synchrony. To study this, we recorded local field potentials in rats treated with anodal tDCS (a-tDCS) after unilateral ischemic motor cortex lesion. To enhance the effect of a-tDCS on neuronal synchrony, we added monopolar pulses (a-tDCSmp) during a treatment. We found that ischemic lesions reduced interhemispheric coherence in the low gamma frequency range. By contrast, a-tDCSmp treatment increased interhemispheric coherence along with motor improvement in a skilled reaching task. These observations indicate that increased neuronal coherence is a likely mechanism by which tDCS improves stroke recovery. Moreover, this work adds to previous evidence that measures of brain coherence could be used as a biomarker of stroke recovery, which may help in the design of more effective tDCS protocols for stroke rehabilitation.

Orexin 1 and orexin 2 receptor antagonism in the basolateral amygdala modulate long-term potentiation of the population spike in the perforant path-dentate gyrus-evoked field potential in rats.

Involvement of amygdalo-hippocampal substructures in patients with narcolepsy due to deficiencies in the orexinergic system, and the presence of hippocampus-dependent memory impairments in this disorder, have led us to investigate the effects of orexin 1 and 2 receptor antagonism in the basolateral amygdala (BLA) on long-term potentiation (LTP) of dentate gyrus (DG) granular cells. We used a 200-Hz high-frequency stimulation protocol in anesthetized rats. We studied the long-term synaptic plasticity of perforant path-dentate gyrus granule cells following the inactivation of orexin receptors before and after tetanic stimulation. LTP of the DG population spike was attenuated in the presence of orexin 1 and 2 receptor antagonism (treatment with SB-334867-A and TCS-OX2-29, respectively) in the BLA when compared to that observed following treatment with dimethyl sulfoxide (DMSO). However, the population excitatory post-synaptic potentials were not affected. Moreover, when orexin 1 and 2 receptors in the BLA were blocked after LTP induction, there were no differences between the DMSO and treatment groups. Our findings suggest that the orexinergic system of the BLA plays a modulatory role in the regulation of hippocampal plasticity in rats.

Acute and chronic pain affects local field potential of the medial prefrontal cortex in different band neural oscillations.

The medial prefrontal cortex is involved in the process of sensory discrimination. In this study, we examined the local field potential activity response to the different stages of pain in the prelimbic cortex (PrL) which is a sub-region of the medial prefrontal cortex. Recent studies revealed extensive information about neural oscillations, but there is limited information on the local field potential profiles for acute or chronic pain, particularly in freely moving animals. This study showed that acute mechanical pain increases alpha oscillation and decreases beta and gamma oscillations before spared nerve injury surgery. Delta oscillation was decreased by chronic pain and gamma oscillation varied with time. However, acute mechanical pain stimulus had no effects on local field potential in rats under mechanical allodynia. Together, our findings provide novel insights into the role of medial prefrontal cortex local field potential activity response to pain stimulus.

N- and L-type calcium channels blocker cilnidipine ameliorates neuropathic pain

Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca2+ channels (VDCCs). We recently reported that a selective N-type VDCC blocker attenuated the spinal long-term potentiation (LTP) of C-fiber-evoked field potentials recorded in the spinal dorsal horn of rats, which served as a model for examining synaptic function during central pain sensitization. In this study, we investigated the effects of cilnidipine on the changes related to neuropathic pain induced by nerve injury. Mechanical allodynia and hyperalgesia were evaluated by von Frey test and pin prick test, respectively. Spinal LTP of C-fiber-evoked field potentials were evaluated by in vivo electrophysiology. Intrathecally administrated cilnidipine attenuated mechanical allodynia and hyperalgesia in the spared nerve injury mouse model. Using in vivo electrophysiology in rats, cilnidipine (10µm) administered spinally inhibited the induction and maintenance of high-frequency stimulation-induced LTP of C-fiber-evoked field potentials, while basal C-fiber-evoked field potentials in naïve rats were unaffected. The basal C-fiber-evoked field potentials in nerve-injured rats were strongly inhibited by cilnidipine. Treatment with a specific N-type VDCC blocker, ω-conotoxin GVIA, which reportedly attenuates C-fiber-evoked field potentials both before and after the induction of LTP, attenuated mechanical allodynia and hyperalgesia in nerve-injured mice. By contrast, an L-type VDCC blocker, nicardipine attenuated only mechanical hyperalgesia, but not mechanical allodynia in nerve-injured mice, and also attenuated the established LTP of C-fiber-evoked field potentials in rats. These results suggested that N-type and L-type VDCC blockers may effectively alleviate the hyperalgesia and allodynia associated with neuropathic pain without affecting normal pain perception.

Inactivation of nucleus incertus impairs passive avoidance learning and long term potentiation of the population spike in the perforant path-dentate gyrus evoked field potentials in rats

Involvement of brainstem nucleus incertus (NI) in hippocampal theta rhythm suggests that this structure might play a role in hippocampal-dependent learning and memory. In the present study we aimed to address if NI is involved in an avoidance learning task as well as dentate gyrus (DG) short-term and long-term potentiation. Lidocaine was injected into the NI to transiently inactivate the nucleus, and control rats received saline. Role of NI was studied in passive avoidance learning (PAL) in 3 memory phases of acquisition, consolidation and retrieval. Levels of hippocampal phosphorylated p70 were also assessed in rats involved in PAL. Perforant path-DG short-term synaptic plasticity was studied upon NI inactivation before the paired-pulse stimulation, and also before or after tetanic stimulation in freely moving rats. It was found that NI inactivation delayed learning and impaired retention in the PAL task, with decreased levels of phosphorylated p70 in the respective groups. However, short-term plasticity was not affected by NI inactivation. But long term potentiation (LTP) of DG population spike was poorly induced with NI inactivation compared to the saline group, and it had no effect on population excitatory post-synaptic potential. Furthermore, when NI was inactivated after the induction of LTP, there was no difference between the saline and lidocaine groups. These observations suggest that NI has a role in PAL task, and its inactivation does not change the perforant path-DG granule cell synaptic input but decreases the excitability of the DG granule cells. Further studies should elucidate direct and indirect paths through which NI might influence hippocampal activity.

Working Memory Event Encoding by Theta and Gamma Oscillation of Multi-Channel Local Field Potentials in Rat Based on Wigner-Ville Distribution

Working Memory Event Encoding by Theta and Gamma Oscillation of Multi-Channel Local Field Potentials in Rat Based on Wigner-Ville Distribution

Synchronous pattern of multi-channel local field potentials in rats anesthesized by propofol

Objective To study the phase coherence mode of multi-channel local field potentials (LFPs) of rats cortex under waking, propofol anesthetized and recovery of righting reflex situations and to apply it to estimate the anesthetic degree. Methods Five male Sprague-Dawley rats were selected and 16-channel micro-electrode matrix were implanted in the prefrontal cortex of the rats. Ten days later, 16-channel electric signals were recorded from waking rats using Cerebus 128 Data Acquisition System. Then the rats were anesthetized with propofol intravenously through the tail vein, with the induction dose of propofol of 10 mg/kg and anesthesia maintenance dose of put and the rat regained consciousness, 16-channel electric signals from anaesthetic rats were recorded. After preprocessing, phase coherence of LFPs was calculated among the data from these three situations. Phase coherences were calculated in each window between each signal channel LFP and reference channel LFP with 200-ms multitaper window sliding from the beginning. Time-varying phase coherence dynamic distribution was available between each channel LFP and reference channel LFP with 25-ms overlapping. Results The results shows that the phase coherence average number in waking situation is less than the number in anesthesia (P<0.05); the phase coherence average number in recovery situation is less than that of anesthesia (P<0.05), it is larger than the number in anesthetic situation on the contrary (P<0.05). Conclusion The result indicates that the no synchronization of the LFPs during the waking-up time was found. High synchronization of the LFPs during the anesthetic period was found, while the degree of synchronization of the LFPs during the recovery time was between that of waking-up time period and anesthetic period. It can be applied to identify anesthetic degree of propofol. Key words: Prefrontal cortex of rats; Anesthetic degree of propofol; Local field potentials; Synchronization

Comparison of Anesthetic Depth Indexes Based on Thalamocortical Local Field Potentials in Rats

Local field potentials may allow a more precise analysis of the brain electrical activity than the electroencephalogram. In this study, local field potentials were recorded in the thalamocortical axis of rats to (i) compare the performance of several indexes of anesthetic depth and (ii) investigate the existence of thalamocortical correlated or disrupted activity during isoflurane steady-state anesthesia. Five rats chronically implanted with microelectrodes were used to record local field potentials in the primary somatosensory cortex and ventroposterolateral thalamic nuclei at six periods: before induction of anesthesia; in the last 5 min of randomized 20-min steady-state end-tidal 0.8, 1.1, 1.4, and 1.7% isoflurane concentrations; and after recovery. The approximate entropy, the index of consciousness, the spectral edge frequency, and the permutation entropy were estimated using epochs of 8 s. A correction factor for burst suppression was applied to the spectral edge frequency and to the permutation entropy. The correlation between the derived indexes and the end-tidal isoflurane was calculated and compared for the two studied brain regions indexes. Coherence analysis was also performed. The burst suppression-corrected permutation entropy showed the highest correlation with the end-tidal isoflurane concentration, and a high coherence was obtained between the two studied areas. The permutation entropy corrected with the classic burst suppression ratio is a promising alternative to other indexes of anesthetic depth. Furthermore, high coherence level of activity exists between the somatosensory cortical and thalamic regions, even at deep isoflurane stages.

Fabrication and testing of polyimide-based microelectrode arrays for cortical mapping of evoked potentials

Modern microfabrication techniques make it possible to develop microelectrode arrays that may be utilized not only in neurophysiological research but also in the clinic, e.g. in neurosurgery and as elements of neural prostheses. The aim of this study was to test whether a flexible microelectrode array is suitable for recording cortical surface field potentials in rats. Polyimide-based microelectrode arrays were fabricated by utilizing microfabrication techniques e.g. photolithography and magnetron sputter deposition. The present microelectrode array consists of eight platinum microelectrodes (round-shaped, Ø: 200 μm), transmission lines and connector pads sandwiched between two thin layers of biocompatible polyimide. The microelectrode arrays were electrochemically characterized by impedance spectroscopy in physiological saline solution and successfully tested in vivo by conducting acute and chronic measurements of evoked potentials on the surface of rat cortex. The arrays proved excellent flexibility and mechanical strength during handling and implantation onto the surface of cortex. The excellent electrochemical characteristics and stable in vivo recordings with high spatiotemporal resolution highlight the potential of these arrays. The fabrication protocol described here allows implementation of several other neural interfaces with different layouts, material selections or target areas either for recording or stimulation purposes.

Interleukin-1β Induces Long-Term Potentiation of C-Fiber Evoked Field Potentials in Spinal dorsal Horn in Rats with Neuropathic Pain

Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), impairs long-term potentiation (LTP) in hippocampus, a synaptic model of memory, while in spinal dorsal horn TNF-α is found to induce LTP of C-fiber evoked field potentials in rats with nerve injury. In the present work the role of IL-1β in the spinal LTP of C-fiber evoked field potentials, which is important for pathological pain, was investigated in both physiological and pathological conditions. We found that spinal application of IL-1β at the concentrations up to 500 ng/ml affected neither basal synaptic transmission mediated by C-fiber nor spinal LTP induced by tetanic stimulation in intact rats. In rats with neuropathic pain produced by spared nerve injury (SNI) or lumbar 5 ventral root transection (L5 VRT), however, IL- 1β at a low concentration (5 ng/ml) induced LTP of C-fiber evoked field potentials. Pretreatment with either p38 MAPK inhibitor (SB203580) or NF-κB inhibitor (PDTC) but not with JNK inhibitor (SP600125) completely blocked LTP induced by IL-1β in SNI rats. Taken together, the results indicated that exogenous IL-1β might induce spinal LTP only in rats with nerve injury but not in intact rats. The differential effects of proinflammatory cytokines on synaptic plasticity in spinal dorsal horn and in hippocampus may be clinically significant.

Depression of C fibre-evoked spinal field potentials by the spinal δ opioid receptor is enhanced in the spinal nerve ligation model of neuropathic pain: Involvement of the μ-subtype

The depression rate of C fibre-evoked spinal field potentials by spinally applied morphine is increased in two states of spinal hyperexcitation, namely the spinal ligation model (SNL) of neuropathic pain and long-term potentiation (LTP) of C fibre-evoked spinal field potentials. This present work sought to determine opioid receptor subtypes involved in such increase in the SNL model.We recorded spinal field potentials during spinal superfusion with increasing, cumulative concentrations of selective subtype-specific agonists in rats subjected to SNL, as well as in non-ligated animals. The μ opioid receptor (MOR) agonist DAMGO significantly depressed field potentials evoked by C (100 nM) or Aδ fibres (1 μM) both in neuropathic and non-ligated rats, whereas the κ receptor opioid (KOR) agonist ±U-50488 was ineffective. The δ opioid receptor (DOR) (D-Ala2)-Deltorphin II was more effective in reducing C fibre-evoked spinal field potentials in rats subjected to SNL (100 nM) than in non-ligated rats (100 μM). Subclinical MOR activation (10 nM DAMGO) produced a leftward shift in (D-Ala2)-Deltorphin II dose–response curve in non-ligated rats (IC50 16.59 ± 0.99 μM vs 120.3 ± 1.0 μM in the absence of DAMGO), and isobolar analysis revealed synergistic interaction (interaction index 0.25). MOR blockade (100 μM CTOP) disinhibited C fibre-evoked potentials in neuropathic, but not in basal animals, and partially impeded DOR depression in both groups. DOR blockade (1 mM naltrindole) was ineffective in either group.We show that DOR-mediated depression of spinal responses to peripheral unmyelinated fibre-input is increased in the SNL model, an increase that is contributed to by positive interaction with the spinal MOR.

Electric stimulation at sciatic nerve evokes long-term potentiation of cornu dorsale medullae spinalis field potential in rats at various developmental phases

Background Long-term potentiation of cornu dorsale medullae spinalis field potential in adult rats has already been reported; however, there is lack of correlated researches on naenonate, infant and adult rats which have different responses to pain conduction information. Objective To observe the various effects of electric stimulation at sciatic nerve on long-term potentiation of evoked field potential at superficial layer of cornu dorsale medullae spinalis of rats at various developmental phases and analyze manifestations of pain conduction information at superficial layers (I___II) of cornu dorsale medullae spinalis in immature rats. Design Grouping controlled study. Setting Department of Physiology, Medical College of Wuhan University. Materials The experiment was carried out in the Laboratory of Physiology (provincial laboratory), Medical College of Wuhan University from March 2006 to May 2007. A total of 27 healthy male Sprague-Dawley (SD) rats, 17–90 days old, SPF grade, weighing 41–200 g, were provided by Experimental Animal Center, Medical College of Wuhan University. Methods Based on their birthdays, rats were divided into naenonate group (17–20 days old, weighing 41–52 g, n =10), infant group (35–50 days old, weighing 87–125 g, n =10) and adult group (60–90 days old, weighing 180–200 g, n =7). Left sciatic nerve was separated and stimulated with single square wave (15 V, 0.5 ms). Meanwhile, evoked field potential was recorded at superficial layers of lateral T 13–L 1 cornu dorsale medullae spinalis and then stimulated with high-frequent and high-intensive tetanizing current (30–40 V, 0.5 ms, 100 Hz, 1 s per bundle, 10 s in bundle interval) four times. After the operation, onset of long-term potentiation was observed; meanwhile, amplitude changes and latency of field potential were analyzed. Main outcome measures Amplitude and latency changes of field potential at superficial layers of cornu dorsale medullae spinalis of rats in the three groups. Results A total of 27 accepted rats were involved in the final analysis. ▪ Amplitude changes: Electric stimulation at sciatic nerve with high-frequent and high-intensive tetanizing current could induce evoked field potential at superficial layers (I___II) of cornu dorsale medullae spinalis in the three groups. Long-term potentiation in the naenonate group manifested that amplitude of A-kind never fiber was raised and there was significant difference ( P < 0.05). In addition, average amplitude was increased and there was obviously significant difference ( P < 0.01). Long-term potentiation in the infant group manifested that amplitude of C-kind never fiber was raised and there was significant difference ( P < 0.01); while, long-term potentiation in the adult group manifested that amplitude of C-kind never fiber was raised and there was significant difference ( P < 0.01). Otherwise, latencies in the three groups were all shortened. ▪ Latency changes: Average latency of A-kind nerve fiber in the naenonate group was shortened and there was significant difference ( P < 0.01); in addition, evoked potential of C-kind nerve fiber was low and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation ( P > 0.05). Average latency of C-kind nerve fiber in the infant group was shortened and there was significant difference ( P < 0.01); in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation ( P > 0.05). Average latency of C-kind nerve fiber in the adult group was shortened and there was significant difference ( P < 0.01); in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation. Conclusion Evoked field potential at superficial layer of cornu dorsale medullae spinalis can be recorded through electric stimulation at sciatic nerve. Single stimulation and tetanizing electric stimulation can cause different characteristics of evoked field potential in rats at various developmental phases. Superficial layer of cornu dorsale medullae spinalis of naenonate rats is mainly caused by A-kind nerve fiber which participants in pain conduction and formation of pain sensitivity; however, that of infant and adult rats mainly depends on C-kind nerve fiber.

Simulation of sleep spindles and spike and wave discharges using a novel method for the calculation of field potentials in rats

We suggest a new method for calculation of extracellular field potentials generated by a large population of pyramidal cells (PCs), using a single PC compartmental model. Similar methods described earlier use the assumption that the intracellular potential or current distributions of the cells within the population are much alike as a result of simultaneous activation at about the same longitudinal location (i.e., all the PCs in the population are located on the same level and are ideally synchronized). However, the degree of synchronization of natural firing even during synchronized rhythmic discharges in the cortex is not as high. We introduce the possibility to vary the degree of synchronization of the PCs’ activity in the population, thus taking into account disperse timing of cortical pyramidal cells’ firing. The temporal variability in cell firing is described by a Gaussian distribution, the width of which defines the degree of synchronization/desynchronization. In addition, the suggested method allows for certain spatial spread of PCs in the population along longitudinal axis of the PCs. The method was applied to test the assumption that the transition from sleep spindles to rhythmic spike and wave discharges (SWDs) observed in absence epilepsy may occur due to an increase in pyramidal cells’ firing synchronization. We show that in case of weak synchronization of PC firing in the population, the shape of field potential during rhythmic thalamic input is similar to the oscillations during a sleep spindle, while at stronger synchronization of PCs, it looks much more as a SWD, with clear expressed spikes and waves. This suggests that in large population of pyramidal cells the changes in the degree of synchronization of cell firing may explain the changes in the shape of field potential from spindle oscillations to SWDs and vice versa.

Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1

The inhibitory activity of gamma-aminobutyric acid (GABA) is considered critical in setting the conditions for synaptic plasticity, and many studies support an important role of GABA in the suppression of nociceptive transmission in the dorsal horn. Consequently, any injury-induced modification of the GABA action has the potential to critically modify spinal synaptic plasticity. We have previously reported that chronic constriction injury of the sciatic nerve was accompanied by long-lasting potentiation of superficial spinal dorsal horn field potentials following high-frequency tetanus. In this study we examined whether the GABA-A receptor agonist muscimol would modify post-tetanic responses in rats with chronic constriction injury. In animals exhibiting maximal thermal hyperalgesia as one sign of neuropathic pain 7 days after loose ligation of the sciatic nerve, spinal application of muscimol (5, 10 or 20 μg) before the high-frequency (50 Hz) tetanus produced a long-lasting depression (rather than potentiation) of spinal dorsal horn field potentials. In separate but related Western immunoblot experiments, we also established that the chronic constriction injury was accompanied by significant decreases in the content of the GABA transporter GAT-1. These data demonstrated that GABA-A receptor agonists may effectively influence the expression of long-lasting synaptic plasticity in the spinal dorsal horn, and that an injury-induced loss in GABA transporter content may have contributed to a depletion of GABA from its terminals within the spinal dorsal horn. These data lent further support to the notion that the loss of GABA inhibition may have important consequences for the development of neuropathic pain.

Stimulus-evoked resetting of the dentate theta rhythm: relation to working memory.

The relationship between memory and rhythmic neural activity in the dentate gyrus was investigated by analyzing spontaneous dentate field potentials in rats performing either a working or reference memory task. The baseline level of rhythmic theta activity was similar in both groups. Following an initial negative potential in the sensory-evoked response, a resetting of the rhythmic activity which was time-locked to the stimulus onset was observed in rats performing the working memory task, but not in rats performing the reference memory task. The results suggest that the resetting of the theta rhythm by behaviorally-relevant stimuli may have an important role in working memory.