Slow state transitions of sustained neural oscillations by activity-dependent modulation of intrinsic excitability.

Little is known about the dynamics and mechanisms of transitions between tonic firing and bursting in cortical networks. Here, we use a computational model of a neocortical circuit with extracellular potassium dynamics to show that activity-dependent modulation of intrinsic excitability can lead to sustained oscillations with slow transitions between two distinct firing modes: fast run (tonic spiking or fast bursts with few spikes) and slow bursting. These transitions are caused by a bistability with hysteresis in a pyramidal cell model.

Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

Objective: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study.

Bursting of thalamic neurons and states of vigilance.

This article addresses the functional significance of the electrophysiological properties of thalamic neurons. We propose that thalamocortical activity, is the product of the intrinsic electrical properties of the thalamocortical (TC) neurons and the connectivity their axons weave. We begin with an overview of the electrophysiological properties of single neurons in different functional states, followed by a review of the phylogeny of the electrical properties of thalamic neurons, in several vertebrate species.

Waking-sleep modulation of paroxysmal activities induced by partial cortical deafferentation.

We investigated the dependency of electrical seizures produced by cortical undercut upon behavioral states of vigilance in chronically implanted cats. Experiments were performed 1-12 weeks after white matter transection. Multisite field potentials and intracellular activity were recorded from suprasylvian and marginal gyri.

Increased propensity to seizures after chronic cortical deafferentation in vivo.

Cortical injury may lead to clinical seizures. We investigated the changing patterns of the sleeplike slow oscillation and its tendency to develop into paroxysmal activity consisting of spike-wave (SW) complexes at 2-4 Hz after partial deafferentation of the suprasylvian gyrus. Experiments were carried out in anesthetized cats, at different time intervals (wk 1 to wk 5, W1-W5) after cortical undercut.

Synaptic plasticity in local cortical network in vivo and its modulation by the level of neuronal activity.

Neocortical neurons maintain high firing rates across all behavioral states of vigilance but the discharge patterns vary during different types of brain oscillations, which are assumed to play an important role in information processing and memory consolidation. In the present study, we report that trains of stimuli applied to local neocortical networks of cats, at frequencies that mimic endogenous brain rhythms, produced depression or potentiation of postsynaptic potentials, which lasted for several minutes. This form of synaptic plasticity was not mediated through NMDA receptors since it persisted after blockade of these receptors, but was strongly modulated by the level of background neuronal activity.

Sleep, epilepsy and thalamic reticular inhibitory neurons.

Thalamic reticular neurons release the potent inhibitory neurotransmitter GABA and their main targets are thalamocortical neurons in the dorsal thalamus. This article focuses on two topics: (i) the role of thalamic reticular neurons in the initiation of spindles, a hallmark oscillation during early sleep stages; and (ii) the reticular-induced inhibition of thalamocortical neurons during cortically generated spike-wave seizures. Although hotly debated during the past decade, the idea of spindle generation by a network of GABAergic reticular neurons was recently supported by in vivo and in computo studies demonstrating interactions between inhibitory reticular neurons that lead to spindle sequences.

The reticular nucleus revisited: intrinsic and network properties of a thalamic pacemaker.

The intrinsic and network properties of thalamic reticular (RE) neurons, which release the potent inhibitory neurotransmitter gamma-aminobutyric acid (GABA), endow them with oscillatory properties within the frequency range of sleep spindles (7-15 Hz), a hallmark brain rhythm that characterizes early sleep stages. The original hypothesis that RE neurons are pacemakers of spindles, based on absence of this oscillation in thalamocortical (TC) systems after disconnection from RE nucleus and presence of spindle rhythmicity in the deafferented RE nucleus, is supported by new experimental results in vivo, in vitro and in computo showing that interactions through chemical synapses as well as electrical coupling among inhibitory RE neurons lead to generation and synchronization of spindle sequences within the nucleus. Besides their pacemaking role in spindle generation, RE neurons are crucially implicated in the inhibition of TC neurons during cortically generated spike-wave (absence) seizures, which may explain the obliteration of signals from the external world and unconsciousness during these epileptic fits.

Synaptic enhancement induced through callosal pathways in cat association cortex.

The corpus callosum plays a major role in synchronizing neocortical activities in the two hemispheres. We investigated the changes in callosally elicited excitatory postsynaptic potentials (EPSPs) of neurons from cortical association areas 5 and 7 of cats under barbiturate or ketamine-xylazine anesthesia. Single pulses to callosal pathway evoked control EPSPs; pulse-trains were subsequently applied at different frequencies to homotopic sites in the contralateral cortex, as conditioning stimulation; thereafter, the single pulses were applied again to test changes in synaptic responsiveness by comparing the amplitudes of control and conditioned EPSPs.

The cortically evoked secondary depolarization affects the integrative properties of thalamic reticular neurons.

Corticothalamic terminals on thalamic reticular (RE) neurons account for most synapses from afferent pathways onto this nucleus and these inputs are more powerful than those from axon collaterals of thalamocortical neurons. Given the supremacy of cortical inputs, we analysed here the characteristics and possible mechanisms underlying a secondary component of the cortically elicited depolarization in RE neurons, recorded in cats under barbiturate anesthesia. Electrical stimulation of corticothalamic axons in the internal capsule evoked fixed and short-latency excitatory postsynaptic potentials (EPSPs) that, by increasing stimulation intensity and at hyperpolarized levels (< -70 mV), developed into low-threshold spikes and spindle oscillations.

Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex.

Chronically isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of post-traumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in chronically isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation.

Membrane bistability in thalamic reticular neurons during spindle oscillations.

The thalamic reticular (RE) nucleus is a major source of inhibition in the thalamus. It plays a crucial role in regulating the excitability of thalamocortical networks and in generating some sleep rhythms. Current-clamp intracellular recordings of RE neurons in cats under barbiturate anesthesia revealed the presence of membrane bistability in approximately 20% of neurons.

Experimental evidence and modeling studies support a synchronizing role for electrical coupling in the cat thalamic reticular neurons in vivo.

Thalamic reticular (RE) neurons are crucially implicated in brain rhythms. Here, we report that RE neurons of adult cats, recorded and stained intracellularly in vivo, displayed spontaneously occurring spikelets, which are characteristic of central neurons that are coupled electrotonically via gap junctions. Spikelets occurred spontaneously during spindles, an oscillation in which RE neurons play a leading role, as well as during interspindle lulls.

Prolonged hyperpolarizing potentials precede spindle oscillations in the thalamic reticular nucleus.

The thalamic reticular (RE) nucleus is a key structure in the generation of spindles, a hallmark bioelectrical oscillation during early stages of sleep. Intracellular recordings of RE neurons in vivo revealed the presence of prolonged hyperpolarizing potentials preceding spindles in a subgroup (30%) of neurons. These hyperpolarizations (6-10 mV) lasted for 200-300 ms and were present just before the onset of spontaneously occurring spindle waves.

Synaptic interactions between thalamic and cortical inputs onto cortical neurons in vivo.

To study the interactions between thalamic and cortical inputs onto neocortical neurons, we used paired-pulse stimulation (PPS) of thalamic and cortical inputs as well as PPS of two cortical or two thalamic inputs that converged, at different time intervals, onto intracellularly recorded cortical and thalamocortical neurons in anesthetized cats. PPS of homosynaptic cortico-cortical pathways produced facilitation, depression, or no significant effects in cortical pathways, whereas cortical responses to thalamocortical inputs were mostly facilitated at both short and long intervals. By contrast, heterosynaptic interactions between either cortical and thalamic, or thalamic and cortical, inputs generally produced decreases in the peak amplitudes and depolarization area of evoked excitatory postsynaptic potentials (EPSPs), with maximal effect at approximately 10 ms and lasting from 60 to 100 ms.

Local gating of information processing through the thalamus.

Inhibitory sculpting of afferent signals in the thalamus is exerted by two types of neurons using gamma-amino butyric acid (GABA) as neurotransmitter. Of them, local-circuit neurons exert their functions via two outputs: axons and presynaptic dendrites. In this issue of Neuron, Govindaiah and Cox reveal that synaptic activation of metabotropic glutamate receptors selectively increases the output of presynaptic dendrites of local interneurons in rat visual thalamus, without affecting the axonal output.

Contribution of intrinsic neuronal factors in the generation of cortically driven electrographic seizures.

Some electrographic seizures are generated intracortically. The cellular and ionic bases of cortically generated spontaneous seizures are not fully understood. Here we investigated spontaneously occurring seizures consisting of spike-wave complexes intermingled with fast runs in ketamine-xylazine anesthetized cats, using dual intracellular recordings in which one pipette contained a control solution and another pipette contained blockers of K(+), Na(+), or Ca(2+) currents.

Acetylcholine systems and rhythmic activities during the waking--sleep cycle.

The two processes of activation in thalamocortical systems exerted by mesopontine cholinergic neurons are (a) a direct depolarization associated with increased input resistance of thalamic relay neurons, which is antagonized by muscarinic blockers, and (b) a disinhibition of the same neurons via hyperpolarization of inhibitory thalamic reticular neurons. Low-frequency (< 15 Hz) oscillations during slow-wave sleep, characterized by rhythmic and prolonged hyperpolarizations, are suppressed by brainstem cholinergic neurons and nucleus basalis cholinergic and GABAergic neurons projecting to thalamic reticular neurons. Fast rhythms (20-60 Hz) appear during the sustained depolarization of thalamic and neocortical neurons during brain-active states that are accompanied by increased release of acetylcholine (ACh) in the thalamus and cerebral cortex.

[Cellular basis of transition between sleep and electrographic seizures].

Epileptic seizures mainly develop during slow-wave sleep. Our experiments, using multi-site, extra- and intracellular recordings, show a transformation without discontinuity from sleep patterns to seizures. The cerebral cortex is the minimal substrate of paroxysms with spike-wave complexes at ~3 Hz.

Hyperexcitability of intact neurons underlies acute development of trauma-related electrographic seizures in cats in vivo.

Cortical trauma can lead to development of electrographic paroxysmal activities. Current views of trauma-induced epileptogenesis suggest that chronic neuronal hyperexcitability and extensive morphological reorganization of the traumatized cortex are required for the generation of electrographic seizures. However, the mechanisms responsible for the initiation of electrographic seizures shortly after cortical injury are poorly understood.

Partial cortical deafferentation promotes development of paroxysmal activity.

This study tested the hypothesis that early functional alterations in neuronal synchrony in the partially deafferented cortex may lead to spontaneously occurring electrographic seizures. In vivo experiments with partial deafferentation of cat suprasylvian gyrus after extensive undercut of the white matter were conducted using multi-site EEG, extracellular unit and intracellular recordings. The amplitudes of EEG waves were much higher in the areas surrounding deafferented cortical fields as compared with control and with undercut cortex.

The corticothalamic system in sleep.

The transition from wakefulness to NREM sleep is associated with typical signs of brain electrical activity, characterized by prolonged periods of hyperpolarization and increased membrane conductance in thalamocortical (TC) neurons, with the consequence that incoming messages are inhibited and the cerebral cortex is deprived of signals from the outside world. There are three major oscillations during NREM sleep. Spindles are generated within the thalamus, due to thalamic reticular (RE) neurons that impose rhythmic inhibitory sequences onto TC neurons, but the widespread synchronization of this rhythm is governed by corticothalamic projections.

Electrophysiological properties and input-output organization of callosal neurons in cat association cortex.

Intracellular recordings from association cortical areas 5 and 7 were performed in cats under barbiturate or ketamine-xylazine anesthesia to investigate the activities of different classes of neurons involved in callosal pathways, which were electrophysiologically characterized by depolarizing current steps. Excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and/or antidromic responses were elicited by stimulating homotopic sites in the contralateral cortical areas. Differential features of EPSPs related to latencies, amplitudes, and slopes were detected in closely located (50 microm or less) neurons recorded in succession along the same electrode track.