Both the thalamocortical and limbic systems generate a variety of brain state-dependent rhythms but the relationship between the oscillatory families is not well understood. Transfer of information across structures can be controlled by oscillations. We suggest that slow oscillation of the neocortex, which was discovered by Mircea Steriade, temporally coordinates the self-organized oscillations in the neocortex, entorhinal cortex, subiculum and hippocampus. Transient coupling between rhythms can guide bidirectional information transfer among these structures and might serve to consolidate memory traces.

We have studied circuit activities in layer IV of rat somatosensory barrel cortex that contains microgyri induced by neonatal freeze lesions. Structural abnormalities in GABA-containing interneurons are present in the epileptogenic paramicrogyral area (PMG). We therefore tested the hypothesis that decreased postsynaptic inhibition within barrel microcircuits occurs in the PMG and contributes to epileptogenesis when thalamocortical afferents are activated. In thalamocortical (TC) slices from naïve animals, single electrical stimuli within the thalamic ventrobasal (VB) nucleus evoked transient cortical multi-unit activity lasting 65 ± 42 msec. Similar stimuli in TC slices from lesioned barrel cortex elicited prolonged (850 ± 100 msec) paroxysmal discharges that originated in the PMG and propagated laterally over several mm. The duration of paroxysmal discharges were shortened by ∼70% when APV was applied and were abolished by CNQX. The cortical paroxysmal discharges did not evoke thalamic oscillations. Whole-cell patch-clamp recordings show that there is a shift in the balance of TC-evoked responses in the PMG that favors excitation over inhibition. Dual, whole-cell recordings in layer IV of the PMG indicated that selective loss of inhibition from fast-spiking interneurons to spiny neurons in the barrel circuits is likely to contribute to unconstrained cortical recurrent excitation with generation and spread of paroxysmal discharges.

As established in early studies, the basalo-cortical system serves as an extra-thalamic relay from the brainstem reticular activating system to the cerebral cortex. As Mircea Steriade documented, activating impulses are transmitted through either the nonspecific thalamo-cortical projection system or the basalo-cortical projection system to stimulate widespread, fast, cortical activity that is characteristic of the activation that occurs naturally during waking (W) and paradoxical sleep (PS) states. However, basal forebrain (BF) neurons are different from thalamic neurons in several ways. First, many cortically projecting BF neurons utilize acetylcholine (ACh), which has a crucial role in stimulating fast cortical activity. Second, ACh-releasing neurons discharge selectively during W and PS and cease firing during slow-wave sleep (SWS). Third, ACh-releasing neurons discharge rhythmically in bursts during cortical activation and can, thus, modulate the cortex in a slow rhythmic manner to facilitate coherent activity across broad cortical networks. Fourth, the rhythmic discharge by BF neurons that release ACh, GABA or glutamate and project to the cortex occurs at respiratory or theta frequencies of the olfactory and limbic cortices, which reveals the particular importance of these inputs as well as outputs within basalo-cortico-basalo circuits. Fifth, other noncholinergic BF neurons, including GABA-releasing neurons, are active selectively during sleep: some of these potentially promote slow-wave activity during SWS through cortical projections; and others might promote behavioral quiescence during SWS and PS through descending projections. Finally, BF neurons also project to the thalamus and might, thus, either recruit or join thalamic neurons in modulating cortical activity across the sleep–waking cycle.

Mircea Steriade exerted a powerful, driving influence on systems neuroscience for nearly five decades. Here, we review the case of a influential individual of another sort: a single thalamocortical (TC) neuron that exerts an extraordinary influence on fast-spike interneurons of somatosensory ‘barrel’ cortex. This cell was studied over a period of several days in an awake rabbit using methods of extracellular cross-correlation. In many ways, the influence of this TC neuron on topographically aligned fast-spike interneurons is typical of TC inputs to these cells, manifested as a fast-rising, very brief increase in postsynaptic spike probability. However, this TC neuron was distinct from other TC neurons studied because of the potency of that influence and the number of interneurons influenced. In one of these recipient interneurons, the probability of spike generation within a narrow window (0.7 msec) following a TC spike was 21%, and this value reached 53% for TC spikes with long preceding interspike intervals (conditions that allow recovery from chronic, activity-dependent depression at the TC synapse). Based on these data, we maintain that, in the awake state, spontaneous spikes of single TC neurons drive some classes of cortical neurons powerfully. Moreover, we suggest that neighboring TC neurons (like neuroscientists) vary greatly in their global ‘driving influence’ on recipient neocortical circuits, and that a few of these cells exert a disproportionate impact on cortical networks.

The paraventricular thalamic nucleus (PVT) receives dense noradrenergic input, but little is known about α2 adrenoceptors (ARs) in this nucleus. We have investigated effects of the agonist α-methyl-norepinephrine (m-NE) on PVT neurons in vitro. Based on their physiological and morphological characteristics, three distinct classes of PVT neurons have been identified. The first class exhibits membrane hyperpolarization on stimulation with m-NE (0.05–25 µM). This hyperpolarizing effect is observed in the presence of tetrodotoxin (TTX; 0.5–1 µM), blocked by yohimbine (1 µM) and mimicked by clonidine (10 µM), which indicates that it is mediated by postsynaptic α2 ARs. Further experiments indicate that it is mediated through an increase in G protein-coupled K+ conductance. In a second class of neurons, m-NE (0.05–25 µM) induces a slow membrane depolarization that is mimicked by phenylephrine (5 µM) and blocked by prazosin (75 nM), which indicates the involvement of α1 ARs. The third class of neurons is insensitive to m-NE (5–25 µM), and has a lower input resistance and a larger dendritic tree compared to the two other classes. The three types of neurons differ in their resting properties, and their firing patterns are changed by m-NE. These findings indicate anatomical and functional specialization of PVT neurons.

The responses of relay cells in the human thalamic ventral caudal nucleus (Vc) was explored in a set of experiments designed to study neuronal firing patterns evoked in humans by pain and thermal cutaneous stimuli. Cells responsive to cold or painful stimuli have been found to produce low threshold spike (LTS) bursting preferentially in response to these stimuli. This appears to be an intrinsic thalamic phenomenon and not a firing pattern produced by input from the periphery. Microstimulation within the Vc during awake surgical procedures demonstrates that cold and pain sensations can be evoked by short bursts of electrical stimuli in a pattern similar to that observed during neuronal LTS bursts. These results strongly suggest that that cold and pain sensations may be mediated in part by human thalamic LTS burst firing patterns.