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.

Disruptions in the thalamocortical circuit have been related to several psychiatric disorders, such as schizophrenia and obsessive-compulsive disorders. The dopaminergic/GABAergic afferents to the limbic thalamocortical circuit originate in the ventral tegmental area (VTA) and play a crucial role in the regulation of the normal cognitive functions mediated by this circuit. Moreover, it has been shown that the dopaminergic modulatory system is altered in schizophrenics. Despite the strong clinical and behavioral evidence of the importance of the thalamocortical circuit and the mesocortical dopamine (DA) system for normal cognitive function, little is known about the basic synaptic interactions between the thalamus and VTA. This research hypothesized that VTA stimulation would evoke DAergic and/or GABAergic-mediated responses in the MD thalamic neurons. Using intracellular recordings in vivo, it was found that VTA stimulation evoked short latency EPSPs in 73% of the recorded MD neurons and IPSPs-like responses in 16% of the MD cells. The nature of the VTA-MD projection was explored using DAergic and GABAergic drugs. It was found that the indirect DAergic agonist amphetamine affects the spontaneous and VTA-mediated responses recorded in the MD thalamus. These results indicate that the VTA projection contributes to the modulation of MD activity and that the disruption of such modulation may be relevant in neuropsychiatry disorders.

In thalamocortical neurons relaying sensory information, we recently described a phosphorylation mechanism that induces a marked increase in the amplitude of the low-voltage activated Ca2+ current (T-type). Surprisingly, potentiation of the T-current closely depends on the state of the channel and is, therefore, both voltage- and ATP-dependent. Further analysis of the modification of channel activity induced by this regulation, and underlying the increase in the macroscopic current amplitude, requires a detailed study of the T-current biophysical properties that, unfortunately, might be constrained by the technical limitations of whole-cell recordings. Therefore, in the present study we have developed an alternative approach that is based on computational models of T-channel activity using Markov gating schemes. We show that both modifications in the activation kinetics of the channels and/or the existence of a second channel population with a conducting state conditioned by a phosphorylation step can explain the specific properties of T-currents that have been observed in thalamocortical neurons as a result of their ATP/voltage-dependent regulation. The flexibility in the T-type current behavior that is incorporated in these models might also help to unravel new roles for T-channels in shaping the different firing properties of thalamocortical neurons.