Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer.

Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia, and examined the effects of local infusion of gap junction blockers on 5-15 Hz oscillations. Local infusion of the gap junction blockers carbenoxolone and mefloquine resulted in significant decreases in the power of oscillations over a 30-min period, but the power of oscillations was unchanged in control experiments following vehicle injections. In addition, infusion of gap junction blockers had no significant effect on multi-unit activity, suggesting that the attenuation of low-frequency oscillations was likely due to reductions in electrical coupling rather than a decreased excitability within the granule cell layer. Our results indicate that electrical coupling among the Golgi cell networks in the cerebellar cortex contributes to the local circuit mechanisms that promote the occurrence of GCL LFP slow oscillations in the anesthetized rat.

Kinematics and muscle activation patterns during a maximal voluntary rate activity in healthy elderly and young adults.

BACKGROUND: Maximal voluntary rate (MVR) performance tasks can provide important age-related information to the limiting factors associated with movement and the development of fatigue. AIM: To determine whether kinematic and muscle activation patterns during an MVR task differ between young and older adults. METHODS: We continuously measured frequency, amplitude, peak velocity, index of co-contraction and median frequencies of the index finger flexors and extensors during a 20-s MVR task in 10 young and 10 older subjects. RESULTS: Index finger amplitude and peak velocity in flexion and extension were significantly lower in the older group. During the MVR, amplitude was maintained in the old (1-4 s, 53.2° ± 2.8° vs. 15-19 s, 48.6° ± 3.2°, ns) but not in the younger group (1-4 s, 64.9° ± 4.9° vs. 15-19 s, 59.4° ± 3.3°; p = 0.001). Frequency declined in the young (1-4 s, 5.2 ± 0.24 Hz vs. 15-19 s, 4.4 ± 0.25 Hz; p = 0.001) and old (1-4 s, 4.6 ± 0.17 Hz vs. 15-19 s, 4.0 ± 0.15 Hz; p = 0.01). Similarly, peak flexion velocity of the young (1-4 s, 1.77 ± 0.07 × 103 °/s vs. 15-19 s, 1.01 ± 0.07 × 103 °/s, p = 0.01) and older groups (1-4 s, 1.04 ± 0.07 × 103 °/s vs. 15-19 s, 0.78 ± 0.06 × 103 °/s; p = 0.016) as well as peak extension velocity of the young (1-4 s, 1.01 ± 0.053 × 103 °/s vs. 15-19 s, 0.78 ± 0.06 × 103 °/s, p = 0.01) and older groups (1-4 s, 0.72 ± 0.04 × 103 °/s vs. 15-19 s, 0.58 ± 0.05 × 103 °/s, p = 0.012) significantly decreased throughout the MVR. Median frequency of the flexors and extensors were maintained and were not different between groups. Only the older group experienced an increase in the index of co-contraction. CONCLUSION: The changes in kinematics over time are not a result of a decrease in pre-post test force or velocity, but rather central factors affecting movement coordination.

Cerebellar Cortex 4-12 Hz Oscillations and Unit Phase Relation in the Awake Rat.

Oscillations in the granule cell layer (GCL) of the cerebellar cortex have been related to behavior and could facilitate communication with the cerebral cortex. These local field potential (LFP) oscillations, strong at 4-12 Hz in the rodent cerebellar cortex during awake immobility, should also be an indicator of an underlying influence on the patterns of the cerebellar cortex neuronal firing during rest. To address this hypothesis, cerebellar cortex LFPs and simultaneous single-neuron activity were collected during LFP oscillatory periods in the GCL of awake resting rats. During these oscillatory episodes, different types of units across the GCL and Purkinje cell layers showed variable phase-relation with the oscillatory cycles. Overall, 74% of the Golgi cell firing and 54% of the Purkinje cell simple spike (SS) firing were phase-locked with the oscillations, displaying a clear phase relationship. Despite this tendency, fewer Golgi cells (50%) and Purkinje cell's SSs (25%) showed an oscillatory firing pattern. Oscillatory phase-locked spikes for the Golgi and Purkinje cells occurred towards the peak of the LFP cycle. GCL LFP oscillations had a strong capacity to predict the timing of Golgi cell spiking activity, indicating a strong influence of this oscillatory phenomenon over the GCL. Phase-locking was not as prominent for the Purkinje cell SS firing, indicating a weaker influence over the Purkinje cell layer, yet a similar phase relation. Overall, synaptic activity underlying GCL LFP oscillations likely exert an influence on neuronal population firing patterns in the cerebellar cortex in the awake resting state and could have a preparatory neural network shaping capacity serving as a neural baseline for upcoming cerebellar operations.

Synchronized gamma oscillations (30-50 Hz) in the amygdalo-hippocampal network in relation with seizure propagation and severity.

In this study, we demonstrate that gamma oscillations (30-50 Hz) recorded in the local field potentials (LFP) of the hippocampus are a marker of temporal lobe seizure propagation and that the level of LFP synchrony in the amygdalo-hippocampal network, during these oscillations, is related to the severity of seizures. Sprague-Dawley rats were given a single systemic dose of kainic acid (KA; 6 mg/kg, i.p.) and local field potential activity (1-475 Hz) of the dorsal hippocampus, the amygdala and the neocortex was recorded. Of 135 ictal discharges, 55 (40.7%) involved both limbic structures. We demonstrated that 78.2% of seizures involving both the hippocampus and amygdala showed hippocampal gamma oscillations. Seizure duration was also significantly correlated with the frequency of hippocampal gamma oscillations (r2=0.31, p<0.01) and LFP synchrony in the amygdalo-hippocampal network (r2=0.21, p<0.05). These results suggest that gamma oscillations in the amygdalo-hippocampal network could facilitate long-range synchrony and participate in the propagation of seizures.

Basal Ganglia: Striosomes and the Link between Motivation and Action.

The basal ganglia integrate motivation and action across their circuits; neurons in anatomical modules called striosomes could contribute strongly to this merger. A new method focusing on network interconnections will allow a better understanding of the functional role of striosomes.

State-Dependent Entrainment of Prefrontal Cortex Local Field Potential Activity Following Patterned Stimulation of the Cerebellar Vermis.

The cerebellum is involved in sensorimotor, cognitive, and emotional functions through cerebello-cerebral connectivity. Cerebellar neurostimulation thus likely affects cortical circuits, as has been shown in studies using cerebellar stimulation to treat neurological disorders through modulation of frontal EEG oscillations. Here we studied the effects of different frequencies of cerebellar stimulation on oscillations and coherence in the cerebellum and prefrontal cortex in the urethane-anesthetized rat. Local field potentials were recorded in the right lateral cerebellum (Crus I/II) and bilaterally in the prefrontal cortex (frontal association area, FrA) in adult male Sprague-Dawley rats. Stimulation was delivered to the cerebellar vermis (lobule VII) using single pulses (0.2 Hz for 60 s), or repeated pulses at 1 Hz (30 s), 5 Hz (10 s), 25 Hz (2 s), and 50 Hz (1 s). Effects of stimulation were influenced by the initial state of EEG activity which varies over time during urethane-anesthesia; 1 Hz stimulation was more effective when delivered during the slow-wave state (Stage 1), while stimulation with single-pulse, 25, and 50 Hz showed stronger effects during the activated state (Stage 2). Single-pulses resulted in increases in oscillatory power in the delta and theta bands for the cerebellum, and in frequencies up to 80 Hz in cortical sites. 1 Hz stimulation induced a decrease in 0-30 Hz activity and increased activity in the 30-200 Hz range, in the right FrA. 5 Hz stimulation reduced power in high frequencies in Stage 1 and induced mixed effects during Stage 2.25 Hz stimulation increased cortical power at low frequencies during Stage 2, and increased power in higher frequency bands during Stage 1. Stimulation at 50 Hz increased delta-band power in all recording sites, with the strongest and most rapid effects in the cerebellum. 25 and 50 Hz stimulation also induced state-dependent effects on cerebello-cortical and cortico-cortical coherence at high frequencies. Cerebellar stimulation can therefore entrain field potential activity in the FrA and drive synchronization of cerebello-cortical and cortico-cortical networks in a frequency-dependent manner. These effects highlight the role of the cerebellar vermis in modulating large-scale synchronization of neural networks in non-motor frontal cortex.

Synchronous, focally modulated beta-band oscillations characterize local field potential activity in the striatum of awake behaving monkeys.

Synchronous oscillatory activity has been observed in a range of neural networks from invertebrate nervous systems to the human frontal cortex. In humans and other primates, sensorimotor regions of the neocortex exhibit synchronous oscillations in the beta-frequency band (approximately 15-30 Hz), and these are also prominent in the cerebellum, a brainstem sensorimotor region. However, recordings in the basal ganglia have suggested that such beta-band oscillations are not normally a primary feature of these structures. Instead, they become a dominant feature of neural activity in the basal ganglia in Parkinson's disease and in parkinsonian states induced by dopamine depletion in experimental animals. Here we demonstrate that when multiple electrodes are used to record local field potentials, 10-25 Hz oscillations can be readily detected in the striatum of normal macaque monkeys. These normally occurring oscillations are highly synchronous across large regions of the striatum. Furthermore, they are subject to dynamic modulation when monkeys perform a simple motor task to earn rewards. In the striatal region representing oculomotor activity, we found that small focal zones could pop in and out of synchrony as the monkeys made saccadic eye movements, suggesting that the broadly synchronous oscillatory activity interfaces with modular spatiotemporal patterns of task-related activity. We suggest that the background beta-band oscillations in the striatum could help to focus action-selection network functions of cortico-basal ganglia circuits.

Diurnal influences on electrophysiological oscillations and coupling in the dorsal striatum and cerebellar cortex of the anesthetized rat.

Circadian rhythms modulate behavioral processes over a 24 h period through clock gene expression. What is largely unknown is how these molecular influences shape neural activity in different brain areas. The clock gene Per2 is rhythmically expressed in the striatum and the cerebellum and its expression is linked with daily fluctuations in extracellular dopamine levels and D2 receptor activity. Electrophysiologically, dopamine depletion enhances striatal local field potential (LFP) oscillations. We investigated if LFP oscillations and synchrony were influenced by time of day, potentially via dopamine mechanisms. To assess the presence of a diurnal effect, oscillatory power and coherence were examined in the striatum and cerebellum of rats under urethane anesthesia at four different times of day zeitgeber time (ZT1, 7, 13 and 19-indicating number of hours after lights turned on in a 12:12 h light-dark cycle). We also investigated the diurnal response to systemic raclopride, a D2 receptor antagonist. Time of day affected the proportion of LFP oscillations within the 0-3 Hz band and the 3-8 Hz band. In both the striatum and the cerebellum, slow oscillations were strongest at ZT1 and weakest at ZT13. A 3-8 Hz oscillation was present when the slow oscillation was lowest, with peak 3-8 Hz activity occurring at ZT13. Raclopride enhanced the slow oscillations, and had the greatest effect at ZT13. Within the striatum and with the cerebellum, 0-3 Hz coherence was greatest at ZT1, when the slow oscillations were strongest. Coherence was also affected the most by raclopride at ZT13. Our results suggest that neural oscillations in the cerebellum and striatum, and the synchrony between these areas, are modulated by time of day, and that these changes are influenced by dopamine manipulation. This may provide insight into how circadian gene transcription patterns influence network electrophysiology. Future experiments will address how these network alterations are linked with behavior.

Linking oscillations in cerebellar circuits.

In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how neuronal groups interact together, organizing for different contexts. The cerebellar cortex harbors a variety of such local circuit rhythms, from the rhythms in the cerebellar cortex per se, or those dictated from important afferents. We present here certain cerebellar oscillatory phenomena that have been recorded in rodents and primates. Those take place in a range of frequencies: from the more known oscillations in the 4-25 Hz band, such as the olivocerebellar oscillatory activity and the granule cell layer oscillations, to the more recently reported slow (<1 Hz oscillations), and the fast (>150 Hz) activity in the Purkinje cell layer. Many of these oscillations appear spontaneously in the circuits, and are modulated by behavioral imperatives. We review here how those oscillations are recorded, some of their modulatory mechanisms, and also identify some of the cerebellar nodes where they could interact. A particular emphasis has been placed on how these oscillations could be modulated by movement and certain neuropathological manifestations. Many of those oscillations could have a definite impact on the way information is processed in the cerebellum and how it interacts with other structures in a variety of contexts.

Synchronization in primate cerebellar granule cell layer local field potentials: basic anisotropy and dynamic changes during active expectancy.

The cerebellar cortex is remarkable for its organizational regularity, out of which task-related neural networks should emerge. In Purkinje cells, both complex and simple spike network patterns are evident in sensorimotor behavior. However, task-related patterns of activity in the granule cell layer (GCL) have been less studied. We recorded local field potential (LFP) activity simultaneously in pairs of GCL sites in monkeys performing an active expectancy (lever-press) task, in passive expectancy, and at rest. LFP sites were selected when they showed strong 10-25 Hz oscillations; pair orientation was in stereotaxic sagittal and coronal (mainly), and diagonal. As shown previously, LFP oscillations at each site were modulated during the lever-press task. Synchronization across LFP pairs showed an evident basic anisotropy at rest: sagittal pairs of LFPs were better synchronized (more than double the cross-correlation coefficients) than coronal pairs, and more than diagonal pairs. On the other hand, this basic anisotropy was modifiable: during the active expectancy condition, where sagittal and coronal orientations were tested, synchronization of LFP pairs would increase just preceding movement, most notably for the coronal pairs. This lateral extension of synchronization was not observed in passive expectancy. The basic pattern of synchronization at rest, favoring sagittal synchrony, thus seemed to adapt in a dynamic fashion, potentially extending laterally to include more cerebellar cortex elements. This dynamic anisotropy in LFP synchronization could underlie GCL network organization in the context of sensorimotor tasks.

Electrical coupling mediates tunable low-frequency oscillations and resonance in the cerebellar Golgi cell network.

Tonic motor control involves oscillatory synchronization of activity at low frequency (5-30 Hz) throughout the sensorimotor system, including cerebellar areas. We investigated the mechanisms underpinning cerebellar oscillations. We found that Golgi interneurons, which gate information transfer in the cerebellar cortex input layer, are extensively coupled through electrical synapses. When depolarized in vitro, these neurons displayed low-frequency oscillatory synchronization, imposing rhythmic inhibition onto granule cells. Combining experiments and modeling, we show that electrical transmission of the spike afterhyperpolarization is the essential component for oscillatory population synchronization. Rhythmic firing arises in spite of strong heterogeneities, is frequency tuned by the mean excitatory input to Golgi cells, and displays pronounced resonance when the modeled network is driven by oscillating inputs. In vivo, unitary Golgi cell activity was found to synchronize with low-frequency LFP oscillations occurring during quiet waking. These results suggest a major role for Golgi cells in coordinating cerebellar sensorimotor integration during oscillatory interactions.

Motor sequence learning in primate: role of the D2 receptor in movement chunking during consolidation.

Motor learning disturbances have been shown in diseases involving dopamine insufficiency such as Parkinson's disease and schizophrenic patients under antipsychotic drug treatment. In non-human primates, motor learning deficits have also been observed following systemic administration of raclopride, a selective D2-receptor antagonist. These deficits were characterized by persistent fluctuations of performance from trial to trial, and were described as difficulties in consolidating movements following a learning period. Moreover, it has been suggested that these raclopride-induced fluctuations can result from impediments in grouping separate movements into one fluent sequence. In the present study, we explore the hypothesis that such fluctuations during movement consolidation can be prevented through the use of sumanirole - a highly selective D2 agonist - if administered before raclopride. Two monkeys were trained to execute a well known sequence of movements, which was later recalled under three pharmacological conditions: (1) no drug, (2) raclopride, and (3) sumanirole+raclopride. The same three pharmacological conditions were repeated with the two monkeys, trained this time to learn new sequences of movements. Results show that raclopride has no deleterious effect on the well known sequence, nor the sumanirole+raclopride co-administration. However, results on the new sequence to be learned revealed continuous fluctuations of performances in the raclopride condition, but not in the sumanirole+raclopride condition. These fluctuations occurred concurrently with a difficulty in merging separate movement components, known as a "chunking deficit". D2 receptors seem therefore to be involved in the consolidation of new motor skills, and this might involve the chunking of separate movements into integrated motor sequences.

Oscillations of local field potentials in the rat dorsal striatum during spontaneous and instructed behaviors.

Oscillatory activity is a candidate mechanism for providing frequency coding for the generation, storage and replay of sequential representations of events and episodes. We recorded local field potentials (LFPs) and spike activity in the striatum, a basal ganglia structure implicated in behavioral action-sequence learning and performance, as rats engaged in spontaneous and instructed behaviors in a T-maze task. We found that during voluntary behaviors, striatal LFPs exhibit prominent theta-band oscillations together with rhythms at higher and lower frequencies. Analysis of the theta-band activity demonstrated that these oscillations are strongly modulated during task performance and increase as the animals choose and execute their turning responses in the cue-instructed T-maze task. These theta rhythms are locally generated and are coherent across large parts of the striatum. We suggest that modulation of oscillatory activity in the striatum may be a key feature of neural processing related to the control of voluntary behavior.

Learning-related coordination of striatal and hippocampal theta rhythms during acquisition of a procedural maze task.

The striatum and hippocampus are conventionally viewed as complementary learning and memory systems, with the hippocampus specialized for fact-based episodic memory and the striatum for procedural learning and memory. Here we directly tested whether these two systems exhibit independent or coordinated activity patterns during procedural learning. We trained rats on a conditional T-maze task requiring navigational and cue-based associative learning. We recorded local field potential (LFP) activity with tetrodes chronically implanted in the caudoputamen and the CA1 field of the dorsal hippocampus during 6-25 days of training. We show that simultaneously recorded striatal and hippocampal theta rhythms are modulated differently as the rats learned to perform the T-maze task but nevertheless become highly coherent during the choice period of the maze runs in rats that successfully learned the task. Moreover, in the rats that acquired the task, the phase of the striatal-hippocampal theta coherence was modified toward a consistent antiphase relationship, and these changes occurred in proportion to the levels of learning achieved. We suggest that rhythmic oscillations, including theta-band activity, could influence not only neural processing in cortico-basal ganglia circuits but also dynamic interactions between basal ganglia-based and hippocampus-based forebrain circuits during the acquisition and performance of learned behaviors. Experience-dependent changes in coordination of oscillatory activity across brain structures thus may parallel the well known plasticity of spike activity that occurs as a function of experience.

Local field potential oscillations in primate cerebellar cortex: synchronization with cerebral cortex during active and passive expectancy.

Many brain regions, such as the cerebellum, primary somatosensory cortex (SI), and primary motor cortex (MI), interact to produce coordinated actions. Synchronization of local field potentials (LFPs) in sensorimotor cerebral areas has been related to motor performance, often through 10- to 25-Hz oscillatory LFPs. The macaque cerebellar paramedian lobule (PM) also shows 10- to 25-Hz LFP oscillations, which are modulated in a stimulus-response lever press task to get reward (active condition), but also, albeit differently, in a similarly timed stimulus-reward relation (passive condition). This study focuses on simultaneous LFP activity in primate SI or MI and the PM cerebellum during the active (left- or right-hand lever presses) and passive conditions. Results show a similar modulation pattern of 10- to 25-Hz oscillations in the cerebellum, MI, and SI during the active condition (left or right hand), decreasing after stimulus onset, returning, and again decreasing after movement onset. In the passive condition, when the monkey did not move but got reward, all 3 areas show an oscillatory profile where oscillations increase after stimulus onset and last until reward, denoting a role for these oscillations in passive expectancy. However, synchronization between cerebellar LFPs and SI LFPs is higher during the active condition than during the passive condition, and highest for the interested hand. This greater PM-SI synchronization, when the monkey had to press the lever, could represent a form of cerebro-cerebellar communication, perhaps to serve somatosensory processing to accomplish the task; PM-MI synchronization was less selective for the hand used and might carry a more general type of information.

Local field potential oscillations in primate cerebellar cortex: modulation during active and passive expectancy.

Cerebellar local field potential (LFP) oscillations were recorded in the paramedian lobule of one hemisphere, while monkeys were in two behavioral conditions: actively performing an elbow flexion-extension or a lever-press task in response to an auditory or visual stimulus to get reward (active condition), or waiting quietly for the reward to come in the same time window after the appearance of the stimulus (passive condition). The oscillations in the paramedian lobule were first characterized in four monkeys, and they showed an idiosyncratic frequency for each monkey, between 13 and 25 Hz. The granule cell layer multi-unit activity was phase-locked with the negative phase of the LFP oscillations, while Purkinje cell simple spikes were also sometimes phase-locked with the LFP. Three monkeys were trained to perform the motor tasks: the LFP oscillations were modulated, in the active condition, in a systematic manner in relation to the lever-press or elbow flexion-extension tasks. During periods when the monkey was waiting to initiate movement, LFP oscillations appeared and then stopped with movement initiation. This modulation was valid for the task being executed with either hand. Surprisingly, the LFP oscillations were also systematically modulated during the passive condition; as the monkey was waiting for the usual time to get a reward passively, oscillations appeared stronger and were stopped by the end of the usual delay, whether the monkey was rewarded or not. This type of modulation was not affected by the length of the stimulus, as long as the reward window was known to the monkey. If the monkey had not been previously trained to the active condition, the modulation appeared in the passive condition. These results show that cerebellar LFP oscillations in the paramedian lobule are reliably present when the monkey is involved in a waiting period, whether this period ends with an active or passive event. This study provides electrophysiological evidence for a specific pattern of activity in the cerebellum for the expectancy of events that are known to be bound to happen, either externally, or from voluntary action.