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Somatosensory cortical neuronal population activity across states of anaesthesia.

Experiments were carried out to learn about changes in sensory cortical processing associated with different levels of anaesthesia. Traditionally this question has been addressed by studying single neurons. Because state changes are likely to influence the relationships between neurons, the present experiments were undertaken to investigate the spatial and temporal firing patterns distributed across cortex. Using 5 x 5 or 10 x 10 microelectrode arrays, spontaneous and stimulus-evoked activity of multineuron clusters was recorded from rat somatosensory 'barrel' cortex (the whisker representation) during a light surgical stage of urethane anaesthesia, and after two supplemental doses of urethane which led to intermediate and deep levels of anaesthesia. At all depths of anaesthesia, spontaneously occurring action potentials at a single electrode tended to be clustered into 'bursts.' With increasing anaesthetic depth, bursts became more prominent and rhythmic, and increasingly synchronized between cortical barrel-columns. Burst frequency decreased and fewer spikes occurred outside bursts, leading to a decrease in the overall spontaneous firing rate. The cortical territory engaged by individual whiskers contracted with increasing depth of anaesthesia, leading to the spatial segregation of whisker representations. At all stages of anaesthesia, whisker stimulation produced the maximal cortical response when delivered close to burst onset. These observations show that ongoing spontaneous activity modulates sensory response properties and makes peripheral tactile information accessible to a cortical territory whose size is determined by the phase of burst cycle. The possible significance of the cyclic cortical responsiveness encountered during urethane anaesthesia to cortical processing in awake rats is considered.

Action Potentials↗

Cortical oscillatory activity during spatial echoic memory.

In human magnetoencephalogram, we have found gamma-band activity (GBA), a putative measure of cortical network synchronization, during both bottom-up and top-down auditory processing. When sound positions had to be retained in short-term memory for 800 ms, enhanced GBA was detected over posterior parietal cortex, possibly reflecting the activation of higher sensory storage systems along the hypothesized auditory dorsal space processing stream. Additional prefrontal GBA increases suggested an involvement of central executive networks in stimulus maintenance. The present study assessed spatial echoic memory with the same stimuli but a shorter memorization interval of 200 ms. Statistical probability mapping revealed posterior parietal GBA increases at 80 Hz near the end of the memory phase and both gamma and theta enhancements in response to the test stimulus. In contrast to the previous short-term memory study, no prefrontal gamma or theta enhancements were detected. This suggests that spatial echoic memory is performed by networks along the putative auditory dorsal stream, without requiring an involvement of prefrontal executive regions.

Acoustic Stimulation↗

Prefrontal cortical up states are synchronized with ventral tegmental area activity.

The innervation of the prefrontal cortex (PFC) by the ventral tegmental area (VTA) has an important role in incentive-motivation and cognitive functions. Although this projection has been extensively studied, the precise actions of its transmitters, dopamine (DA) and GABA, on PFC pyramidal neurons remain to be determined. We have recently shown that VTA stimulation elicits a sustained depolarization in PFC pyramidal neurons resembling the periodic depolarizations (up states) these neurons exhibit. This response was shortened by a D1 antagonist, suggesting that DA may sustain depolarized up states in PFC neurons. Here, we tested whether spontaneous PFC up states in vivo require spontaneous VTA activity. Intracellular recordings from PFC neurons conducted simultaneously with VTA local field potentials (LFPs) revealed PFC membrane potential fluctuations occurring synchronously with VTA field potential transitions. Extracellular PFC recordings performed simultaneously with VTA LFPs also indicated a high coherence between these two regions, with VTA oscillations trailing PFC oscillations by a few milliseconds. Furthermore, blockade of VTA activity with lidocaine transiently eliminated PFC LFPs, but not PFC cell up states; instead, up states became irregular during intra-VTA lidocaine administration. These results suggest that baseline levels of VTA activity are necessary for synchronizing PFC pyramidal neurons in the up-down oscillations observed in the anesthetized preparation, allowing the emergence of slow EEG components.

Action Potentials↗

Movement-related event-related desynchronization in neuropsychiatric disorders.

The analysis of event-related desynchronization (ERD) and event-related synchronization (ERS) provides information on the dynamics of cortical activation during cognitive and motor tasks and has been applied in a variety of neurological and psychiatric disorders. In this chapter, we focus on studies concerning movement-related activity, which showed changes in amount, topography, or time course in relation to not only involvement of the motor system--such as Parkinson's disease (PD), dystonia, and stroke affecting the sensorimotor (SM) pathways--but also physiological aging, degenerative dementia, obsessive-compulsive disorder (OCD), and fatigue associated with multiple sclerosis (MS). In these disorders, the extent of abnormality in the pattern of ERD/ERS is related to the severity of the underlying pathology. Moreover in MS, a correlation with the severity of brain tissue has been found. While there is consistency in changes related to ipokinetic disorders, mainly consisting of delayed appearance of ERD to movement preparation, changes occurring in other brain disorders need to be replicated or raise doubts on the specificity of changes across different diseases. Further studies are needed in order to validate the usefulness of this methodology in the assessment of the single patient for diagnosis and monitoring of the natural course of the disease and of treatment efficacy.

Cortical Synchronization↗

Pattern of cortical activity, degree of synchronization, binocular fusion, and binocular rivalry.

The synchronization hypothesis is the likely idea for the binding problem in the brain. Here we tested whether the theory is applicable for the occurrence of either binocular fusion or binocular rivalry. We first showed patterns of activated patches in V1 with proceeding from fusion to rivalry on the basis of Hubel and Wiesel's 1979 illustration. We then assumed that the strength of synchrony between the patches in the left-eye and right-eye ocular dominance columns is a crucial determinant for the divergence between fusion and rivalry. By using the strength of fusion between the paired images as a measure of degree of synchrony, we confirm the assumption about interocular vision and the synchronization hypothesis as well.

Form Perception↗

Postsynaptic variability of firing in rat cortical neurons: the roles of input synchronization and synaptic NMDA receptor conductance.

Neurons in the functioning cortex fire erratically, with highly variable intervals between spikes. How much irregularity comes from the process of postsynaptic integration and how much from fluctuations in synaptic input? We have addressed these questions by recording the firing of neurons in slices of rat visual cortex in which synaptic receptors are blocked pharmacologically, while injecting controlled trains of unitary conductance transients, to electrically mimic natural synaptic input. Stimulation with a Poisson train of fast excitatory (AMPA-type) conductance transients, to simulate independent inputs, produced much less variability than encountered in vivo. Addition of NMDA-type conductance to each unitary event regularized the firing but lowered the precision and reliability of spikes in repeated responses. Independent Poisson trains of GABA-type conductance transients (reversing at the resting potential), which simulated independent activity in a population of presynaptic inhibitory neurons, failed to increase timing variability substantially but increased the precision of responses. However, introduction of synchrony, or correlations, in the excitatory input, according to a nonstationary Poisson model, dramatically raised timing variability to in vivo levels. The NMDA phase of compound AMPA-NMDA events conferred a time-dependent postsynaptic variability, whereby the reliability and precision of spikes degraded rapidly over the 100 msec after the start of a synchronous input burst. We conclude that postsynaptic mechanisms add significant variability to cortical responses but that substantial synchrony of inputs is necessary to explain in vivo variability. We suggest that NMDA receptors help to implement a switch from precise firing to random firing during responses to concerted inputs.

Action Potentials↗

Submillisecond synchronization of fast electrical oscillations in neocortex.

Fast electrical oscillations (FOs; >200 Hz) in the sensory neocortex can be recorded in a variety of species, including humans, and may reflect extremely fast integration of sensory information. This report demonstrates that, in the whisker representation of rat cortex, multivibrissa stimulation produces propagating FO field potential patterns and time-locked unit activity that are sensitive to submillisecond delays in interstimulus intervals. We propose that FOs may be produced by synchronized population spikes and their subthreshold sequelas in cortical pyramidal cells. FOs serve to accurately mark stimulus onset as a phase-encoded excitatory signal, producing phase-sensitive interactions that, in the context of exploratory whisking, may extract features of an object under exploration.

Action Potentials↗

Spontaneous synchronous synaptic calcium transients in cultured cortical neurons.

The firing pattern displayed by neuronal aggregates is thought to play a key role in cortical development and physiology. In this study, we have employed optical recording of intracellular calcium to monitor activity of multiple neurons simultaneously in primary cortical cultures. With this approach, we have observed spontaneous synchronous calcium transients among adjacent cortical neurons. These transients appear to be mediated by prominent spontaneous synaptic excitation, as they are enhanced by picrotoxin, a blocker of inhibitory GABAergic transmission, and reduced by antagonism of glutamate receptors or addition of TTX. After picrotoxin treatment, the calcium transients exhibit regular frequency and amplitude, and occur in synchrony with bursts of excitatory synaptic potentials every 10-20 sec. Using electrical stimulation, we have identified a relative refractory period, extending up to 5 sec after a synchronous burst, that may play a role in cell synchronization. NMDA receptor antagonists or reduced extracellular calcium levels lower the amplitude of the calcium transients yet fail to alter their frequency, suggesting that intracellular calcium levels may not be a major determinant of burst frequency. In contrast, mild depolarization with kainic acid (0.5-1 microM) increased burst frequency up to fivefold, suggesting a critical dependence of rhythmic activity on membrane potential. Chronic blockade of electrical activity with TTX beginning a few days after plating of cultures dampens the amplitude and significantly increases the frequency of calcium transients in mature cultures. These studies demonstrate that aggregates of cultured cortical neurons express synchronous firing activity in vitro and that this network activity is dependent in part on neuronal firing during development.

2-Amino-5-phosphonovalerate↗

Spike frequency adaptation affects the synchronization properties of networks of cortical oscillations.

Oscillations in many regions of the cortex have common temporal characteristics with dominant frequencies centered around the 40 Hz (gamma) frequency range and the 5-10 Hz (theta) frequency range. Experimental results also reveal spatially synchronous oscillations, which are stimulus dependent (Gray & Singer, 1987; Gray, Konig, Engel, & Singer, 1989; Engel, Konig, Kreiter, Schillern, & Singer, 1992). This rhythmic activity suggests that the coherence of neural populations is a crucial feature of cortical dynamics (Gray, 1994). Using both simulations and a theoretical coupled oscillator approach, we demonstrate that the spike frequency adaptation seen in many pyramidal cells plays a subtle but important role in the dynamics of cortical networks. Without adaptation, excitatory connections among model pyramidal cells are desynchronizing. However, the slow processes associated with adaptation encourage stable synchronous behavior.

Action Potentials↗

Spontaneous, synchronous electrical activity in neonatal mouse cortical neurones.

Spontaneous [Ca2+]i transients were measured in the mouse neocortex from embryonic day 16 (E16) to postnatal day 6 (P6). On the day of birth (P0), cortical neurones generated widespread, highly synchronous [Ca2+]i transients over large areas. On average, 52% of neurones participated in these transients, and in 20% of slices, an average of 80% participated. These transients were blocked by TTX and nifedipine, indicating that they resulted from Ca2+ influx during electrical activity, and occurred at a mean frequency of 0.91 min(-1). The occurrence of this activity was highly centred at P0: at E16 and P2 an average of only 15% and 24% of neurones, respectively, participated in synchronous transients, and they occurred at much lower frequencies at both E16 and P2 than at P0. The overall frequency of [Ca2+]i transients in individual cells did not change between E16 and P2, just the degree of their synchronicity. The onset of this spontaneous, synchronous activity correlated with a large increase in Na+ current density that occurred just before P0, and its cessation with a large decrease in resting resistance that occurred just after P2. This widespread, synchronous activity may serve a variety of functions in the neonatal nervous system.

Aging↗

Neurological and behavioral toxicity of kryptopyrrole in the rat.

Ten rats were given 9.1 to 82 mg/kg of 2,4-dimethyl-3-ethylpyrrole (kryptopyrrole) and the behavioral and electroencephalographic effects were studied. Kryptopyrrole was found to decrease EEG voltage, disrupt synchronization and induce abnormal spiking at a variety of cortical sites. Intermittent periods of low frequency hypersynchronous EEG activity was consistently elicited by kryptopyrrole. These waves bear a resemblance to the hypersynchronous EEG patterns associated with hallucinatory agents such as LSD-25. Marked behavioral alterations were observed following the initial injection including ataxia, hyperventilation, locomotor depression and catelepsy. Kryptopyrrole causes major central nervous system dysfunction, and these findings are discussed in the context of a drug-induced model of psychoses.

Animals↗

The effect of microinjections of clonidine into the locus coeruleus on cortical EEG in rats.

Microinjections of clonidine into the locus coeruleus (LC) area synchronized rat cortical EEG. This effect of clonidine was attenuated by local pretreatment of rats with idazoxan, an alpha-2 adrenoceptor antagonist. The data indicate functional role of alpha-2 adrenoceptors within LC area in regulation of ceruleocortical activity, and point at the LC as one of brain targets for the sedative action of clonidine.

Animals↗