Intrathalamic oscillations related to sleep and epilepsy depend on interactions between synaptic mechanisms and intrinsic membrane excitability. One intrinsic conductance implicated in the genesis of thalamic oscillations is the H-current – a cationic current activated by membrane hyperpolarization. Activation of H-current promotes rebound excitation of thalamic relay neurons and can thus enhance recurrent network activity.

We examined the effects of H-current modulation on bicuculline-enhanced network oscillations (2–4 Hz) in rat thalamic slices. The adrenergic agonist norepinephrine, a known regulator of H-current, caused an alteration of the internal structure of the oscillations – they were enhanced and accelerated as the interval between bursts was shortened. The acceleration was blocked by the β-adrenergic antagonist propranolol. The β-agonist isoproterenol mimicked the effect of norepinephrine on oscillation frequency and truncated the responses suggesting that a β-adrenergic up-regulation of H-current modifies the internal structure (frequency) of thalamic oscillations. Consistent with this, we found that H-channel blockade by Cs+ or ZD7288 could decelerate the oscillations and produce more robust (longer lasting) responses. High concentrations of either Cs+ or ZD7288 blocked the oscillations.

These results indicate that a critical amount of H-current is necessary for optimal intrathalamic oscillations in the delta frequency range. Up- or down-regulation of H-current alter not only the oscillation frequency but also retard or promote the development of thalamic synchronous oscillations. This conclusion has important implications regarding the development of epilepsy in thalamocortical circuits.

The effects of different dendritic geometries and distal dendritic Na+ current distributions on the propagation of action potentials (APs) and sensory EPSPs were investigated using a multi-compartment model of thalamocortical (TC) neurones where the somatic and proximal dendritic distribution of voltage-gated channels matched the ones measured experimentally, i.e. a uniform distribution of K+ currents and a non-uniform distribution of Na+ and T-type Ca2+ currents.

Our simulations indicated that the distal dendritic Na+ channel density has not to be larger than 50% of the somatic density in order to reproduce the electrical activities recorded experimentally from the soma and proximal dendrites of TC neurones. Moreover, we could highlight the existence of a distinct threshold density of distal dendritic Na+ channels necessary to support the regeneration of APs in this part of the dendritic tree: this threshold density was smaller for non-branching than for heavily branching dendrites.

The amplitude of the somatic EPSP mainly depended on the number of simultaneously activated synapses on any dendritic branch, despite large differences in the size of the dendritic EPSPs. The amplitude of the EPSP on a proximal dendrite was also dependent on the number and relative location of simultaneously activated synapses on all other proximal dendritic branches. The dendritic geometry did not affect these features of the simulated sensory EPSPs. In addition, the duration of somatic and proximal dendritic EPSPs was markedly increased (100%) in the presence of somatic and proximal dendritic T-type Ca2+ current.

The backpropagation of EPSPs to distal dendrites was affected by the dendritic Na+ channel distributions, but even in the absence of distal dendritic Na+ channels the EPSP reached the dendritic ends with less than 40% decrease in amplitude. Overall, the amplitude of the backpropagating EPSP was not greatly affected by the dendritic geometry, though a smaller amplitude reduction in unbranched than in heavily branching dendrites was observed.

The thalamus of the spiny rat Proechimys guyannensis (casiragua), a common rodent of the Amazon basin, was investigated with immunohistochemistry, using as markers GABA and glutamic acid decarboxylase, and calcium binding proteins. As in all mammals, GABAergic neurons containing also parvalbumin filled the reticular nucleus, and GABAergic cells were seen in the dorsal lateral geniculate nucleus. At variance with the laboratory rat, GABAergic and parvalbumin-containing neurons were also seen in the laterodorsal and anterodorsal nuclei, in which the two markers were co-distributed. Calbindin-immunopositive cells were widely distributed in dorsal thalamic domains, except for the intralaminar nuclei, and prevailed in the laterodorsal nucleus. The distribution of calretinin-immunopositive neurons was more restricted, and they were especially concentrated in the laterodorsal and midline nuclei.

At variance with the laboratory rat, in which systemic pilocarpine administration induces status epilepticus and results in chronic limbic epilepsy, pilocarpine elicited in casiragua an acute seizure that was not followed by spontaneous seizures up to 1 month, when changes were evaluated in the thalamus using also image analysis. Parvalbumin immunostaining in reticular nucleus neurons and in the dorsal thalamus neuropil, and the number of parvalbumin-positive and GABAergic cells in the laterodorsal and anterodorsal nuclei, exhibited an increase with respect to controls. Calbindin immunostaining was also enhanced, whereas calretinin immunostaining was mostly reduced, but was preserved in midline neurons. The findings show, after an acute seizure induced in an animal model of anti-convulsant mechanisms, regional long-term neurochemical alterations that could reflect functional changes in inhibitory and excitatory thalamic neurons.

In a systematic study of thalamocortical relay neuron responses to sinusoidal current injection [J. Neurophysiol. 83 (1), 588], we found that the Fourier fundamental of tonic responses was regularly phase advanced during low temporal frequency stimulation (1/10 cycle at 0.1 Hz). We hypothesized that such phase advances of the Fourier fundamental response were due to a slow spike-frequency adaptation. Here we measure the time-dependence of the instantaneous firing rate during a current pulse protocol, confirm the presence of a slow spike-frequency adaptation, and quantify the adaptation time constant (0.6–2.0 s) and percentage adaptation of spike rate (40–60%). In light of these results, we augment a previously reported minimal integrate-and-fire-or-burst (IFB) neuron model with an adaptation current. When the parameters for this current are fit using a quantitative theory of spike-frequency adaptation [J. Neurophysiol. 79, 1549], the IFB model reproduces the experimentally observed phase advance of the Fourier fundamental response during sinusoidal current injection. Using fast-slow variable analysis, we develop a firing-rate reduction of the IFB model and perform parameter studies to investigate the dependence of the Fourier fundamental response (amplitude and phase) on the maximum conductance and recovery time constant for the adaptation current. Analytical calculations clarify the relationship between dc and ac measures of the suppression of response due to spike-frequency adaptation, show how the latter depends on stimulation frequency, and confirm the adaptation-induced phase advance of the Fourier fundamental observed in both experiment and simulation.

Voltage-activated calcium channels in thalamic neurons are considered important elements in the generation of thalamocortical burst firing during periods of electroencephalographic synchronization. A potent counterpart of calcium-mediated depolarization may reside in the activation of calcium-dependent potassium conductances. In the present study, thalamocortical relay cells that were acutely disso-ciated from the rat ventrobasal thalamic complex (VB) were studied using whole-cell patch-clamp techniques. The calcium-dependent potassium-current (IK(Ca)) was evident as a slowly activating component of outward current sensitive to the calcium ions (Ca2+)-channel blocker methoxyverapamil (10 μM) and to substitution of external calcium by manganese. The IK(Ca) was blocked by tetraethylam-monium chloride (1 mM) and iberiotoxin (100 nM), but not apamin (1 μM). In addition, isolated VB neurons were immunopositive to anti-α(913–926) antibody, a sequence-directed antibody to the a-subunit of “big” Ca2+-dependent K+-channel (BKCa) channels. Activators of the adenylyl cyclase cyclic adenosine monophosphate (cAMP) system, such as forskolin (20 μM), dibutyryl-cAMP (10 mM) and 3-isobutyl-1 -methylxanthine (500 μM), selectively and reversibly suppressed IK(Ca). These results suggest that a rise in intracellular cAMP level leads to a decrease in a calcium-dependent potassium conductance presumably mediated via BKCa type channels, thereby providing an additional mechanism by which neurotransmitter systems are able to control electrogenic activity in thalamocortical neurons and circuits during various states of electroencephalographic synchronization and de-synchronization.

We studied the synchronous cortical and thalamic activities induced by low (0.5–1 mM) and high (50–100 mM) concentrations of the K+ channel blocker 4-aminopyridine (4AP) in a rat thalamocortical preparation. The presence of reciprocal thalamocortical connectivity was documented by diffusion of the fluorescent tracer Di-IC18 between the somatosensory cortex and the ventrobasal complex (VB) of the thalamus in vitro. Functional reciprocal connectivity was also demonstrated by stimulating the cortical middle-deep layers (which elicited orthodromic responses in VB) or the VB (which induced orthodromic and antidromic responses in the cortex). Spontaneous field potentials were not recorded in either the thalamus or cortex in control medium. Low concentrations of 4AP produced local spindle-like rhythmic oscillations in cortex and VB (duration = 0.4–3.5 s; frequency = 9–16 Hz). In contrast, high concentrations of 4AP induced widespread ictal-like epileptiform discharges (duration = 8–45 s) characterised by lsquo ‘tonic’ component followed by a period of ‘clonic’ discharges in both cortex and VB. Spindle-like activity was abolished in cortex and thalamus by applying the excitatory amino acid receptor antagonist kynurenic acid in VB. In contrast, the same procedure exacerbated ictal-like discharges, while depressing VB activity. Our results indicate that thalamus and cortex can produce synchronous activities in this in vitro thalamocortical network: spindle-like rhythmic oscillations are generated at the thalamic level and imposed upon the cortical network whereas ictal-like discharges have a cortical origin and are modulated by the thalamic network activity. In addition, we have shown that it is possible to preserve reciprocal projections between cortex and thalamus in an in vitro rat slice preparation that could be a valuable tool to study epileptic-prone rat strains.