Thalamic relay neurons have homogeneous, adult-like firing properties and similar morphology by 12 days postnatally (PN 12). Parafascicular (Pf) neurons have a different morphology compared with typical thalamic relay neurons, but the development of their electrophysiological properties is not well studied. Intracellular recordings in PN 12–50 Pf neurons revealed several heterogeneous firing patterns different from those in thalamic relay neurons. Two types of cells were identified: Type I cells displayed a fast afterhyperpolarization (AHP) followed by a large-amplitude, slow AHP; whereas Type II cells had only a fast AHP. These cell types had overlapping membrane properties but differences in excitability. Some properties of Pf neurons were adult-like by PN 12, but, unlike thalamic relay neurons, there were significant maturational changes thereafter, including decreased action potential (AP) duration, increased fast AHP amplitude and increased excitability. Pf neurons did not exhibit rhythmic bursting and generally lacked low-threshold spike (LTS) responses that characterize thalamic relay neurons. Pf neurons exhibited non-linear I-V relationships, and only a third of the cells expressed the time and voltage-dependent hyperpolarization activated (Ih) current, which declined with age. These results indicate that the morphological differences between Pf neurons and typical thalamic relay neurons are paralleled by electrophysiological differences, and that Pf membrane properties change during postnatal development.

Layer 4 of the mouse somatosensory (barrel) cortex has a diversity of interneuron cell types. Tonic inhibition in other regions is cell type-specific and mediated, in part, by δ-subunit containing, extrasynaptic, GABAA receptors. We have investigated tonic inhibition in LTS cells, a major type of inhibitory neuron, and excitatory cells in layer 4 of the mouse barrel cortex using 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridine-3-ol (THIP), a superagonist of these receptors. Bath application of 20 µM THIP produced baseline shifts, which indicates activation of tonic inhibition of both excitatory and LTS cells. The baseline shift was significantly larger in LTS cells. This finding of greater induced current in LTS cells was paralleled by a significantly greater increase in conductance with THIP application in LTS cells. The increase in conductance resulted in LTS cells requiring more current to reach threshold. Because of the differential effects of tonic inhibition on LTS cells and excitatory cells, bath application of THIP increased the network excitability, measured by multi-unit recordings. Thus, the network effect of tonic inhibition in horizontal layer 4 circuits is a paradoxical increase in excitation.

The over-inhibition of thalamic relay cells by hyperactivity of the internal part of the globus pallidus is a cornerstone of the parkinsonian pathophysiology that leads to a distortion of the thalamocortical dynamics called thalamocortical dysrhythmia (TCD). Here, we present the results of the stereotactic pallidothalamic tractotomy (PTT), which interrupts selectively the enhanced pallidal output to the thalamus in a restricted location in the fields of Forel. This operation represents a reactualization of Spiegel's campotomy. PTT was offered to 41 patients (66.1±8.5 years) suffering from chronic, therapy-resistant Parkinson's disease. It was performed bilaterally in 21 patients. Forty patients displayed mixed, i.e. tremulent and akinetic parkinsonian signs, and seven had drug-induced dyskinesias. One patient had only rest tremor. The evaluation was based on the Unified Parkinson's Disease Rating Scale (UPDRS) scores, comparing the patients' preoperative medicated state with the state at the last postoperative follow-up. We, thus, tested surgical success in terms of superiority to drug treatment. Mean follow-up was 22.4 months with 15 patients followed for >2 years. Mean improvement was 60% (P<0.001) for UPDRS III and 51% (P<0.001) for UPDRS II. Significant improvement (P<0.001) appeared in subscores for tremor (87%), limb akinesia (58%) and axial akinesia (33%). Improvement of postural stability and gait was at the limit of significance (P<0.05). Improvement of hypomimia and hypophonia did not reach statistical significance. Increase of dysarthria was significant (P<0.01). Intake of L-DOPA was reduced significantly and 21 patients were able to stop intake. Median improvement of the Quality of Life score was 67%. Improvement remained, independent of follow-up length. In conclusion, PTT provides a high, stable level of relief to parkinsonian patients whose condition cannot be controlled with pharmacotherapy. The rationale of the surgical therapy is based on a selective extrathalamic regulation of the parkinsonian TCD.

This study examines the temporal properties of geniculocortical and corticogeniculate (CG) pathways that link the lateral geniculate nucleus (LGN) and primary visual cortex in the ferret. Using electrical stimulation in the LGN to evoke action potentials in geniculocortical and CG axons, results show that conduction latencies are significantly faster in geniculocortical neurons than in CG neurons. Within each pathway, axonal latency and visual physiology support the view of sub-classes of neurons. By examining the timing of visual responses and the latency of CG feedback, estimates indicate that visual information can reach the cortex and return to the LGN as early as 60 msec following the onset of a visual stimulus. These findings place constraints on the functional role of corticogeniculate feedback for visual processing.

Cerebro–cerebellar interactions are becoming progressively more focused in their anatomical substrate but their functional meaning is still elusive. Here, we review current data on the cerebellar influence on cortical function, with special emphasis on the importance of the cerebellar input for cortical processing in primary motor and sensorimotor areas. Differences in the intracortical processing of cerebellar information are described and the possible role of the thalamus in controlling cerebro–cerebellar loops discussed.

Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe childhood epileptic disorder, is characterized by episodes of seizure with alternating epochs of spike-wave and fast run discharges. In a detailed computational model that incorporates extracellular potassium dynamics, we studied the dynamics of these state transitions between slow and fast oscillations. We show that dynamic modulation of synaptic transmission can cause termination of paroxysmal activity. An activity-dependent shift in the balance between synaptic excitation and inhibition towards more excitation caused seizure termination by favoring the slow oscillatory state, which permits recovery of baseline extracellular potassium concentration. We found that slow synaptic depression and change in chloride reversal potential can have similar effects on the seizure dynamics. Our results indicate a novel role for synaptic dynamics during epileptic neural activity patterns.

We compared the developmental periods in the mouse when projections from the two eyes become segregated in the dorsal lateral geniculate nucleus with the time when this nucleus becomes innervated by cholinergic fibers from the brainstem. Changes in labeling patterns of different tracers injected into each eye revealed that segregation of retinogeniculate inputs commences at postnatal day five (P5) and is largely complete by P8. Immunocytochemical staining showed that cholinergic neurons are present in the parabrachial region of the brain stem on the day of birth. However, cholinergic fibers are not evident in the geniculate until P5, and these are sparse at this age, increasing in density to form well-defined clusters by P12. These results indicate that segregation of eye-specific projections during normal development is unlikely to be regulated by cholinergic inputs from the brainstem.