Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients

Deep brain stimulation (DBS) requires precise localization, which is especially difficult at the thalamus, and even more difficult in anesthetized patients. We aimed to characterize the neurophysiological properties of the ventral intermediate (V.im), ventral caudal (V.c), and centromedian parvo (Ce.pc) and the magnocellular (Ce.mc) thalamic nuclei. We obtained microelectrode recordings from five patients with refractory epilepsy under general anesthesia. Somatosensory evoked potentials recorded by microelectrodes were used to identify the V.c nucleus. Trajectories were reconstructed off-line to identify the nucleus recorded, and the amplitude of the action potential (AP) and the tonic (i.e., mean frequency, density, probability of interspike interval) and phasic (i.e., burst index, pause index, and pause ratio) properties of the pattern discharges were analyzed. The Mahalanobis metric was used to evaluate the similarity of the patterns. The mean AP amplitude was higher for the V.im nucleus (172.7 ± 7.6 µV) than for the other nuclei, and the mean frequency was lower for the Ce.pc nucleus (7.2 ± 0.8 Hz) and higher for the V.c nucleus (11.9 ± 0.8 Hz) than for the other nuclei. The phasic properties showed a bursting pattern for the V.c nucleus and a tonic pattern for the centromedian and V.im nuclei. The Mahalanobis distance was the shortest for the V.im/V.c and Ce.mp/Ce.pc pairs. Therefore, the different properties of the thalamic nuclei, even for patients under general anesthesia, can be used to positively define the recorded structure, improving the exactness of electrode placement in DBS.

Synaptic Drive to Motoneurons During Fictive Swimming in the Developing Zebrafish

The development of swimming behavior and the correlated activity patterns recorded in motoneurons during fictive swimming in paralyzed zebrafish larvae were examined and compared. Larvae were studied from when they hatch (after 2 days) and are first capable of locomotion to when they are active swimmers capable of capturing prey (after 4 days). High-speed (500 Hz) video imaging was used to make a basic behavioral characterization of swimming. At hatching and up to day 3, the larvae swam infrequently and in an undirected fashion. They displayed sustained bursts of contractions (‘burst swimming’) at an average frequency of 60–70 Hz that lasted from several seconds to a minute in duration. By day 4 the swimming had matured to a more frequent and less erratic “beat-and-glide” mode, with slower (∼35 Hz) beats of contractions for ∼200 ms alternating with glides that were twice as long, lasting from just a few cycles to several minutes overall. In whole cell current-clamp recordings, motoneurons displayed similar excitatory synaptic activity and firing patterns, corresponding to either fictive burst swimming (day 2–3) or beat-and-glide swimming (day 4). The resting potentials were similar at all stages (about −70 mV) and the motoneurons were depolarized (to about −40 mV) with generally non-overshooting action potentials during fictive swimming. The frequency of sustained inputs during fictive burst swimming and of repetitive inputs during fictive beat-and glide swimming corresponded to the behavioral contraction patterns. Fictive swimming activity patterns were eliminated by application of glutamate antagonists (kynurenic acid or 6-cyano-7-nitroquinoxalene-2,3-dione anddl-2-amino-5-phosphonovaleric acid) and were modified but maintained in the presence of the glycinergic antagonist strychnine. The corresponding synaptic currents underlying the synaptic drive to motoneurons during fictive swimming could be isolated under voltage clamp and consisted of cationic [glutamatergic postsynaptic currents (PSCs)] and anionic inputs (glycinergic PSCs). Either sustained or interrupted patterns of PSCs were observed during fictive burst or beat-and-glide swimming, respectively. During beat-and-glide swimming, a tonic inward current and rhythmic glutamatergic PSCs (∼35 Hz) were observed. In contrast, bursts of glycinergic PSCs occurred at a higher frequency, resulting in a more tonic pattern with little evidence for synchronized activity. We conclude that a rhythmic glutamatergic synaptic drive underlies swimming and that a tonic, shunting glycinergic input acts to more closely match the membrane time constant to the fast synaptic drive.

Characteristics of antidromically identified oculomotor internuclear neurons during vergence and versional eye movements

1. Previous studies have shown that midbrain near response cells that increase their activity during convergent eye movements project to medial rectus motoneurons, which also increase their activity during convergence. Most neurons in the abducens nucleus decrease their firing rate during convergence, and the source of this vergence signal is unknown. Oculomotor internuclear neurons (OINs) in monkeys project primarily from the medial rectus subdivisions of the oculomotor nucleus to the contralateral abducens nucleus, although there is a smaller ipsilateral projection as well. Because of these anatomic connections, it has been suggested that the OIN input may be responsible for the vergence signal seen on abducens neurons. The behavior of the OINs during eye movements and their synaptic drive are not known. Thus the goal of this study is to determine the behavior of these neurons during conjugate and disjunctive eye movements and to determine if these neurons have an excitatory or inhibitory drive on the abducens neurons. 2. Single-unit recording studies in alert rhesus monkeys were used to characterize the behavior of OINs. Eighteen OINs were identified by antidromic activation and collision testing. The recorded OINs displayed a burst-tonic pattern of activity during adducting saccades, and the majority of these cells displayed an increase in tonic activity with convergent eye movements. 3. Identified OINs were compared with a large sample of non-activated and untested horizontal burst-tonic cells in the medial rectus subdivisions of the oculomotor nucleus. The results indicate that the OINs behave similarly to medial rectus motoneurons during vergence and versional eye movements. None of the OINs displayed vertical eye position sensitivity. 4. Microstimulation of the oculomotor nucleus where both the OINs and medial rectus motoneurons were located resulted in a large adducting twitch of the ipsilateral eye and a smaller abducting twitch of the contralateral eye. The latter effect was presumed to be the result of OIN innervation of the contralateral abducens nucleus. This result suggests that the crossed OIN pathway is predominately, if not entirely, excitatory. 5. Injection of 10% lidocaine HCl into the medial rectus subdivision of the oculomotor nucleus caused a reversible inactivation of the medial rectus motoneurons and OINs. As expected, the inactivation of medial rectus motoneurons resulted in an exophoria and weakness of adduction for the eye ipsilateral to the lidocaine injection. In addition, the lidocaine injection resulted in hypometric and slowed abducting saccades in the eye contralateral to the injection site. This result also suggest that the crossed OIN pathway is excitatory.(ABSTRACT TRUNCATED AT 400 WORDS)