Background spike activity of cerebellar nucleus interpositus neurons in rats

Using computer analysis of the background spike activity recorded from cell units of the cerebellar nucleus interpositus, it was possible to distinguish several dynamic types and regularity gradings that specifically characterize these neurons, and to correlate these characteristics with the statistical parameters of their activity.Translated from Neirofiziologiya, Vol. 25, No. 2, pp. 98–100, March–April, 1993.     

Configurational and volumetric changes of the early prenatal human cerebellar dentate nucleus.

The three-dimensional configurational and volumetric changes of the human dentate nucleus (DN) during intrauterine life were examined in 11 fetuses (11 to 27-28 weeks of gestation). During intrauterine life, the dentate nuclear profile successively passes through the pongid, cercopithecus and prosimian phases of configuration. The smooth, elongated, crescent-shaped DN of 11 weeks lies along a dorsal-ventral axis. A 45 degrees clockwise shift in the position of the nucleus changes the axis to dorsomedial-ventrolateral at 14-15 weeks, which is maintained in subsequent ages. The formation of gyri is preceded by a thinning of the substantia grisea. This begins at 17-18 weeks in the dorso-medial region of the DN. Gyri first make their appearance at 24-25 weeks. The DN of 27-28 weeks resembles the adult human DN. Two regions are discernible at this stage--a microgyric, magnocellular region and a macrogyric, parvocellular region. The DN volume increases with increasing gestational age. Between 14-15, 19-20 and 24-25 weeks the volumetric increase is statistically significant. This is simultaneously accompanied by a modification of the configuration of the DN.     

Precentral neuron activity associated with ipsilateral forelimb movements in monkeys.

Unit activity was recorded in motor cortex on one side, while monkeys were moving left or right fingers, wrists, or arms. On hundred and eighty five movement-related neurons were obtained from two monkeys. Of these, 122 were related to contralateral movements, 50 were to movements of both sides, and the remaining 13 to ipsilateral movements. It was found that ipsilateral-movement-related neurons tended to appear in groups of neurons that were related more to arm movements than to finger and/or wrist movements.     

Patterns of spatio-temporal correlations in the neural activity of the cat motor cortex during trained forelimb movements

In order to study how neurons in the primary motor cortex (MI) are dynamically linked together during skilled movement, we recorded simultaneously from many cortical neurons in cats trained to perform a reaching and retrieval task using their forelimbs. Analysis of task-related spike activity in the MI of the hemisphere contralateral to the reaching forelimb (in identified forelimb or hindlimb representations) recorded through chronically implanted microwires, was followed by pairwise evaluation of temporally correlated activity in these neurons during task performance using shuffle corrected cross-correlograms. Over many months of recording, a variety of task-related modulations of neural activities were observed in individual efferent zones. Positively correlated activity (mainly narrow peaks at zero or short latencies) was seen during task performance frequently between neurons recorded within the forelimb representation of MI, rarely within the hindlimb area of MI, and never between forelimb and hindlimb areas. Correlated activity was frequently observed between neurons with different patterns of task-related activity or preferential activity during different task elements (reaching, feeding, etc.), and located in efferent zones with dissimilar representation as defined by intracortical microstimulation. The observed synchronization of action potentials among selected but functionally varied groups of MI neurons possibly reflects dynamic recruitment of network connections between efferent zones during skilled movement.     

Effect of electric stimulation of the dentate nucleus on focal complexes of epileptic activity in the cerebral cortex

Acute experiments on cats were made with the use of an experimental multifocal epileptic complex (MEC) which was created by local application of different concentrations of penicillin to different zones of the neocortex. At the early stages of the MEC the epileptic activity in the seizure foci increased during electrical stimulation (ES, 100-300 Hz) of the contralateral dentate nucleus. As the epileptic activity of the MEC descended up to the disappearance of some of the dependent foci, ES elicited the suppression of the epileptic discharges in the remaining foci. ES of the dentate nucleus did not affect the overall duration of MEC existence. It is inferred that the dentate nucleus belongs to the antiepileptic system of the brain.     

DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer's disease

Background

The low-density lipoprotein receptor related protein 1 (LRP1) has been implicated in Alzheimer's disease (AD) but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1.

Results

We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP), which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b). Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression.

Conclusions

These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered early in disease. Genetic and functional studies have implicated both LRP1 and NYGGF4 in obesity and cardiovascular disease and the physical association of these proteins may reflect a common mechanism. This is particularly interesting in light of the dual role of ApoE in both cardiovascular risk and AD. The results support further studies on the functional relationship between NYGGF4 and LRP1.     

Brief communication: Proportions of the ventral half of the cerebellar dentate nucleus in humans and great apes

In a previous study about volume comparisons of the cerebellar complex in some hominoid species (1997), progressive development of only the lateral zone group of nuclei was found in the human cerebellar complex. This development was considered to be related not to bipedalism, but to versatile and coordinated finger movement, evolving after bipedalism was established. It was also considered a prerequisite for the evolution of human language. The lateral zone groups of nuclei are represented by the dentate nucleus. Therefore, the present study reports the development of the dentate nucleus in humans in comparison with that in some great apes. One finding is that the average value of ratios for nucleus size of the ventral half (v) to the dorsal half (d) (v/d) was found to be 2.11 in humans, while it was 1.64 in great apes. This finding shows that the greater part of progressive development of the dentate nucleus in humans is due to the development of its ventral half. Therefore, the fiber connection to the frontal association area from the cerebellar cortex, which is involved in the performance of higher cerebellar functions such as cognitive and language functions, would be mediated by the ventral half of the dentate nucleus.     

Single unit activity in the guinea-pig cochlear nucleus during sleep and wakefulness.

The effects of waking and sleep on the response properties of auditory units in the ventral cochlear nucleus (CN) were explored by using extracellular recordings in chronic guinea-pigs. Significant increases and decreases in firing rate were detected in two neuronal groups, a) the "sound-responding" and b) the "spontaneous" (units that do not show responses to any acoustic stimuli controlled by the experimenter). The "spontaneous" may be considered as belonging to the auditory system because the corresponding units showed a suppression of their discharge when the receptor was destroyed. The auditory CN units were characterized by their PSTH in response to tones at their characteristic frequency and also by the changes in firing rate and probability of discharge evaluated during periods of waking, slow wave and paradoxical sleep. The CNS performs functions dependent on sensory inputs during wakefulness and sleep phases. By studying the auditory input at the level of the ventral CN with constant sound stimuli, it was shown that, in addition to the firing rate shifts, some units presented changes in the temporal probability of discharge, implying central actions on the corresponding neurons. The mean latency of the responses, however, did not show significant changes throughout the sleep-waking cycle. The auditory efferent pathways are postulated to modulate the auditory input at CN level during different animal states. The probability of firing and the changes in the temporal pattern, as shown by the PSTH, are thus dependent on both the auditory input and the functional brain state related to the sleep-waking cycle.     

Pattern formation in the cerebellar cortex.

The cerebellar cortex is subdivided rostrocaudally and mediolaterally into a reproducible array of zones and stripes. This makes the cerebellum a valuable model for studying pattern formation in the vertebrate central nervous system. The structure of the adult mouse cerebellar cortex and the series of embryological events that generate the topography are reviewed.     

Characteristics of unit responses of the cat cerebellar cortex to acoustic stimuli

Investigation of unit responses of the cerebellar cortex (lobules VI–VII of the vermis) to acoustic stimulation showed that the great majority of neurons responded by a discharge of one spike or a group of spikes with a latent period of 10–40 msec and with a low fluctuation value. Neurons identified as Purkinje cells responded to sound either by inhibition of spontaneous activity or by a "climbing fiber response" with a latent period of 40–60 msec and with a high fluctuation value. In 4 of 80 neurons a prolonged (lasting about 1 sec or more), variable response with a latent period of 225–580 msec was observed. The minimal thresholds of unit responses to acoustic stimuli were distributed within the range from –7 to 77 dB, with a mode from 20 to 50 dB. All the characteristics of the cerebellar unit responses studied were independent of the intensity, duration, and frequency of the sound, like neurons of short-latency type in the inferior colliculi. In certain properties — firing pattern, latent period, and threshold of response — the cerebellar neurons resemble neurons of higher levels of the auditory system: the medial geniculate body and auditory cortex.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 3–12, January–February, 1973.     

Improved histological localization of GABA-transaminase activity in rat cerebellar cortex after aldehyde fixation.

A method for the chemical fixation of the enzyme GABA-transaminase in nervous tissue is described. It is shown that after perfusion with a formaldehyde/glutaraldehyde fixative, activity of the enzyme in cerebellar cortex is demonstrable whilst cellular morphology is preserved. Results from the improved technique have shown new sites of GABA-transaminase activity in cerebellar cortex. In view of these results a special function for glial cells in this area of brain has been suggested.     

Spontaneous unit activity in the rabbit limbic cortex

Spontaneous unit activity in different parts of the limbic cortex, recorded extracellularly in waking rabbits during chronic experiments, was analyzed. Attention was paid particularly to unit activity in theta- and delta-rhythms. Theta-modulation was found in a small proportion (5–12%) of neurons in all parts except the lateral entorhinal cortex. Delta-activity was found in all structures tested but its characteristics varied. In the subiculum (45% of neurons) it consists of short, high-frequency discharges with long pauses, in the entorhinal cortex (22%) opposite characteristics were found (long loosely packed bursts with short intervals between them). Activating influences raised the frequency and increased the resistance of the theta component and desynchronized the delta volleys in the subiculum and most other structures; in the entorhinal cortex under these circumstances the density of the volleys of spikes was increased but without any change in their frequency or regularity. The spectral composition of unit activity in the presubiculum was mixed. The nature of rhythmic modulation of unit activity in areas of the limbic cortex is discussed.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 16, No. 6, pp. 753–760, November–December, 1984.     

Influences of cerebellar interpositus nucleus and fastigial nucleus on neuronal activity of lateral hypothalamic area

Stimulation of cerebellar interpositus nucleus and (astigial nucleus could influence the neuronal activi-ty of lateral hypothalamic area in the cat, and some of the neurons which respond to the cerebellar stimulations are glucose-sensitive neurons. These results suggest that the cerebellum is involved not only in motor control, but also in the regulation of non-somatic functions through the cerebello-hypothalamic pathways.