Stimulation Of Pontine Nuclei Research Articles

Signals from the Brainstem Sleep/Wake Centers Regulate Behavioral Timing via the Circadian Clock

Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN), the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

Hippocampal theta rhythm induced by rostral pontine nucleus stimulation in the conditions of pedunculopontine tegmental nucleus inactivation

Theta rhythm in rat hippocampus occurs during cortical activation in different forms of waking as well as during paradoxical phase of sleep. The multi-level regulatory system of theta, based mainly on cholinergic transmission, includes structures from the forebrain to the medulla. Among them the most important are two reticular nuclei: the pedunculopontine tegmental nucleus (PPN) and rostral pontine tegmental nucleus (RPO). Functional relations between these two nuclei are still unidentified. It is known that cholinergic stimulation of these nuclei with carbachol leads to induction of theta in the hippocampus. Electrical stimulation has the same effect but only when applied to the RPO. In our experiments, performed on urethanized rats, each of these two methods was applied to the RPO with the PPN being inactivated in the contralateral hemisphere. We found that inactivation of the PPN does not suppress theta induced with carbachol microinjection into the RPO, but completely blocks theta induction with electrical stimulation of the RPO. The results suggest the important role of the PPN in theta rhythm generation from brainstem level, depending on the method of theta rhythm induction, i.e. cholinergic or electric stimulation of the RPO.

Synaptic influences of pontine nuclei on cochlear nucleus cells

Using the in vitro isolated whole brain preparation of the guinea pig, we tested the synaptic effects induced by the stimulation of pontine nuclei (PN) in intracellularly recorded and stained principal cells of the cochlear nucleus (CN). Twenty percent of the recorded cells in all CN subdivisions responded to stimulation of either ipsilateral or contralateral PN, and 12% of the cells exhibited convergence of inputs from both sides. The responses were recorded only in stellate cells of the ventral CN and in the pyramidal cells of the dorsal CN, whereas no responses were observed in bushy, octopus, and giant cells. PN stimulation produced excitatory and inhibitory postsynaptic potentials as well as mixed responses. The heterogeneous nature and the wide latency range (3.2-18 ms) of observed responses suggest significant variability in the underlying synaptic mechanisms and the implicated pathways. We propose that PN projections to the CN, terminating mainly in the granule cell domain (GCD), together with other non-auditory and auditory inputs contribute to multimodal convergence in the GCD leading ultimately to modulatory actions on the output activity of CN principal cells.

The role of the cerebellar cortex in the retention of the conditioned eyeblink response with the stimulation of the dorsolateral pontine nuclei as a conditioned stimulus

The present study assessed the effects of lesions of cerebellar cortex on conditioned responses (CRs) using stimulation of the pontine nuclei as a conditioned stimulus (CS). Seven male New Zealand albino rabbits were implanted with stimulating electrodes in and around the dorsolateral pontine nuclei (DLPN). They were then trained to DLPN stimulation-airpuff pairings until they acquired the classically conditioned eyeblink response. Following training, the animals were given a lesion of the paramedian, ansiform, and Larsell’s HVI lobule. They were then retrained to DLPN stimulation. These animals relearned in 1–9 days. One animal with damage to the interpositus nucleus (IP) neither reacquired to DLPN stimulation nor learned to a tone conditioned stimulus (CS). Together with previous studies from our laboratory, these results suggest that the cerebellar cortex plays an important, though not essential, role in the retention of classically conditioned eyeblink responses to tone, light, lateral reticular nucleus stimulation or pontine nucleus stimulation. However, rabbits in the present study did require significantly longer to reach a stable level of performance after the lesion than they did before the lesion, suggesting that the cerebellar cortex plays a particularly important role in DLPN-stimulation conditioning.

Very short-term potentiation of climbing fiber effects on deep cerebellar nuclei neurons by conditioning stimulation of mossy fiber afferents

Field potentials induced in deep cerebellar nuclei by the electrical stimulation of contralateral red, pontine and reticularis tegmenti pontis oralis nuclei, the restiform body and the inferior olive were recorded in the alert cat. Recording sites in interpositus and fastigial nuclei were selected with the aid of antidromic field potentials induced by red nucleus and restiform body stimulation, respectively. Pontine and reticularis tegmenti pontis oralis nuclei stimulation induced small, but constant amplitude, field potentials consisting of one or two negative waves. Control field potentials induced by inferior olive stimulation consisted of a negative wave at 2-3 ms followed by a late (4-6 ms) positivity. Conditioning stimuli applied to the pontine and reticularis tegmenti pontis oralis nuclei greatly enhanced the amplitude of the inferior olive-evoked synaptic field potential for a time window of about 40 ms. In contrast, inferior olive conditioning stimulation failed to modify the field potentials induced by pontine nuclei stimulation. These facilitatory effects on field potential amplitude showed no long-lasting modifications. The transient modification of inferior olive-induced field potentials could be related to attentional movements made by the animal to natural or electrically-induced sensory cues.

Active avoidance behavior using pontine nucleus stimulation as a conditioned stimulus in the rat

Five groups of rats were trained in an active avoidance task in a shuttle box with different conditioned stimuli. Animals with either a light-conditioned stimulus or with electrical stimulation of the ventral pontine nucleus as a conditioned stimulus rapidly learned to avoid an aversive event, while those with no conditioned stimulus, with electrical stimulation of the lateral pontine nucleus or the medial lemniscus did not learn to avoid. Therefore, stimulation of a specific subdivision of the pontine nucleus is as effective as a light-conditioned stimulus to learn an active avoidance task.

Classical nictitating membrane conditioning in rabbits with varying interstimulus intervals and direct activation of cerebellar mossy fibers as the CS

The rate and level of classical nictitating membrane (NM)/eyelid conditioning in rabbits established by pairing a pontine nucleus stimulation conditioned stimulus (CS) with an air puff unconditioned stimulus (US) were studied at 6 interstimulus intervals (ISIs). Similar to earlier studies which used peripheral CSs, an inverted U-shaped function relating ISI and conditioning was generated. Interstimulus intervals of 250 and 500 ms produced the highest levels of conditioning, 100, 1000 and 2000 ms ISIs resulted in lower levels of conditioning, and no conditioning was established with a 50 ms ISI. These results demonstrate that a normal ISI function can be established when direct activation of cerebellar mossy fibers is used as a CS instead of conventional peripheral CSs.

Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus.

Classical conditioning of skeletal muscle responses was accomplished by pairing microstimulation of the pontine nuclei as a conditioned stimulus (CS) with microstimulation of the dorsal accessory olive as an unconditioned stimulus (US). A conditioned response identical in form to the behavioral response elicited by the olivary stimulation was established when the CS was forward paired with the US, and behavioral extinction occurred with CS-alone presentations or unpaired CS-US presentations. Conditioned responding could not be established or maintained when the CS and US were simultaneously presented or when the US preceded the CS (i.e., backward paired). Complete lesions of the interpositus nucleus abolished both conditioned and unconditioned responses. These findings support the idea that plasticity associated with classical conditioning of skeletal muscle responses occurs in regions of the cerebellum that receive convergent CS and US input.

Morphology of layer V pyramidal neurons in the cat somatosensory cortex: an intracellular HRP study

Pyramidal tract (PT) or corticopontine neurons of the cat somatosensory cortex (SI) were identified with antidromic activation on stimulation of the bulbar pyramid or pontine nuclei (PN) and stained intracellarly with HRP after examining the electrophysiological properties. Comparison of the conduction velocity of the stem axons and the soma-dendritic morphology revealed that in the cat SI, there exists two types of layer V pyramidal neurons, i.e. one has smooth apical dendrites with larger soma (51.6 ± 9.5 × 22.7 ± 2.8 μm) and the other has richly spinous apical dendrites with smaller soma (34.0 ± 8.8 × 15.3 ± 3.3 μm). The former group responded antidromically at latencies shorter than 1 ms by PT stimulation or 1.5 ms by PN stimulation, respectively. These values were consistent with the borderline latencies between two similar groups of layer V pyramidal neurons in the motor (fast and slow PTNs) and parietal (aspiny and spiny layer V corticopontine neurons) cortices in the cat.

Responses evoked in the cerebellar cortex by pontine stimulation.

1. Responses in the cat cerebellar cortex evoked by the pontine stimulation were recorded and analysed with microelectrode trackings in the cortex. Silver ball electrodes freely attachable to the cortical surface were also used to complement the microelectrode analysis.2. The analysis of laminar field potentials in the cerebellar cortex elicited by the pontine nucleus stimulation revealed that responses appeared at a short latency of about 1msec are due to pure mossy fibre volleys and, consequently, the nucleus sends direct mossy fibres to the cerebellar cortex.3. The conduction velocity of ponto-cerebellar mossy fibres could be estimated to be of about 30m/sec at maximum and possibly about 10m/sec on the average, distributing rather widely when compared with that of, for instance, lateral reticular nucleus mossy fibres.4. The mossy fibre responses to the pontine nucleus stimulation appeared most markedly in the lateral part of the cerebellar cortex on the contralateral side though sharp discriminative localization of the ponto -cerebellar projection could not be found by stimulating various foci of the nucleus and by recording from different parts of the cortex.5. The pontine nucleus stimulation often produced the climbing fibre responses in the cerebellar cortex at a latency of 5-10msec. Much more powerful responses through climbing fibres were provoked at a latency of 5-8msec by the stimulation of the pontine tegmentum. By the experimental procedure cutting along the midline between the inferior olives on both sides, it was concluded that the climbing fibre responses set up from both the pontine nucleus and the tegmentum were mediated by the inferior olive.6. The presumed climbing fibre responses of a short latency of 3-4msec were encountered, although seldom, by stimulating the border region between the pontine nucleus and the tegmentum, suggesting existence of some direct climbing fibres from the pontine region to the cerebellar cortex.7. The stimulation of the cerebral motor cortex and the analyses of laminar field potentials in the cerebellar cortex ascertained that the stimulation produced the early mossy fibre responses at a latency of about 3msec and the late climbing fibre ones at a latency of about 10msec. They could be mediated by the pontine nucleus and the inferior olive respectively.