Characteristics of activity of "fast" and "slow" Purkinje cells of the cerebellum

In the guinea pig cerebellar cortex, three types of Purkinje cells were identified according to the properties of complex spikes: fast, intermediate, and slow cells. Fast Purkinje cells have following properties as compared with slow Purkinje cells: (i) salient components with short intervals in complex impulses (on the average, five components with a period of about 2 ms versus two components with a period of about 4 ms); (ii) a short duration of simple spikes (in the average, 2.13 +/- 0.53 ms versus 3.9 +/- 0.65 ms) and a quick restoration of their amplitude after preceding simple spikes (in the mean, 2.83 +/- 0.75 ms versus 11.0 +/- 2.82 ms); and (iii) a more pronounced rebound in the auto-correlation histogram of simple spikes (3.09 +/- 2.12 versus 1.45 +/- 0.36) and a short-latency excitation of simple spikes after complex spikes (2.81 +/- 1.64 versus 1.26 +/- 0.52). A decrease of interspike intervals in simple spike activity of all Purkinje cells was revealed (5.25 +/- 2.71 ms versus 9.71 +/- 3.48 ms in activity fragments without complex spikes). It is supposed that the properties of complex spikes depend on the type of Purkinje cells and may be one of the basic factors determining the interactions between the inputs of climbing and parallel fibers in Purkinje cells.     

Maturation of the activity of cerebellar Purkinje cells and the lift reaction

In experiments on guinea pigs (from newborn to adults), studies have been made on the extensor, support and lift reactions, as well as on the activity of cerebellar Purkinje cells in the same animals. First signs of immature lift, extensor and support reactions were observed already 12th after birth. At this period, mean discharge frequency in Purkinje cells was significantly lower than in the adult animals, reaching 11.5 +/- 1.2 imp/s for simple spikes and 0.45 +/- 0.05 imp/s for complex ones. Complete maturation of lift, extensor and support reactions takes place to the beginning of the 2nd week (8-9 days) of postnatal life. Within this period, significant changes in the activity of Purkinje cells were observed: mean discharge frequency of simple and complex spikes increased correspondingly up to 17.9 +/- 2.3 and 1.48 +/- 0.25 imp/s. At the same time, the mean discharge frequency in Purkinje cells, the average duration of inhibition pause, and the response latency became more stable.     

Activity of the climbing fiber innervating various Purkinje cells

Low-amplitude potentials (10-130 microV) related to the action of a distant branch of the climbing fiber, which elicits complex spikes of the reference Purkinje cell were revealed by means of potential averaging synchronously with complex spikes of Purkinje cells in 10 out of 255 paired records of cerebellar Purkinje cells activity and extracellular field potentials at interelectrode distances of 200-1500 microns. These potential waves had a stable form in independent sets of data. In 3 out of 10 cases, the low-amplitude potentials included a slow (about 100 ms in duration) component. In one case, both test and reference electrodes recorded both simple and complex spikes of different Purkinje cells so that complex spikes of both cells were practically synchronous (conditional probability of complex spikes p = 0.97, onset time difference 0.54 ms). Thus for the first time in cerebellar physiology both simple and complex spikes activity of two Purkinje cells controlled by the same climbing fiber was recorded.     

The number of active Purkinje cells in the microelectrod track as an indicator of maturity of the cerebellum motor function in precocial- and altricial-born animals

In experiments on 5 age groups of anesthetized guinea pigs (from newborns to 4 weeks of postnatal ontogenesis), activity of cerebellum Purkinje cells (PC) (IV-VII lobules of cerebellar vermis) was studied in the single track of microelectrode passing through cell layers. It has been shown that as early as several hours after birth, in the superficial layer of cerebellar cortex, there are recorded occasional background-active, but functionally mature PC represented by simple and complex spikes and accordingly reflecting synaptic PC activation by afferent inputs of mossy and climbing fibers. The functional manifestation of the guinea pig motor behavior at this period of ontogenesis is act of their standing. At this period of ontogenesis, in the newborn and one-day old guinea pigs, from 1 to rarely 11 active PC are recorded, on average, in the single microelectrode track. At the one-week age, the highest number active PC in the track somewhat increases, predominantly at the expense of the mean from the total number of the cells in the track. In the 2-week old guinea pigs the mean number of active PC in the track somewhat falls, while in the 4-week old and adult animals exceeds again, although slightly of the maximal number of PC in the track of newborn animals. The relatively high number of active PC at the very initial period of postnatal ontogenesis can indicate importance of motor function in the congenital food-procuring reflex.     

Functional Role of Cerebellar Purkinje Cells in Ontogenesis of Postural-Motor Reactions in Mature- and Immature-Born Mammals

In experiments on guinea pigs, cats, and rats of different ages, from newborns to adults, the postural and stato-kinetic reflexes were studied with subsequent recording of electrical activity of identified cerebellar Purkinje cells (PC) in the same animals. Simultaneously in same age group of the animals, a morphometrical study of the shape and size of Purkinje cells and their nuclei was carried out. The first signs of manifestation of reflexes of standing and of the support reaction were observed in mature-born guinea pigs as early as at the first day after birth. At this time the PC fire has an irregular and low-frequency character with long inhibitory pauses and a great dispersion of the frequency-time characteristics. In the course of postnatal ontogenesis the parameter of the ratio of frequencies of simple and complex spikes increased in all the studied animals, guinea pigs, rat puppies, and kittens, but to different degrees. The complete maturation of the PC activity in the mature-born guinea pigs took 3–4 weeks after birth, whereas in the immature-born rat puppies and kittens this process took, on average, 5–6 and 8–9 weeks, respectively. By this time, all the studied postural-motor reactions were formed. The comparison of the course of formation of the frequency-time characteristics of the Purkinje cell activity in mature- (guinea pigs) and immature-born (rats and cats) animals allowed establishing that the highest rate of maturation of the Purkinje cell activity in the mature-born animals is observed during the first half, whereas in immature-born animals, during the second half of postnatal ontogenesis. A similar rate of changes also took place at maturation of postural-motor reflexes. The complete functional maturity of the Purkinje cell occurred, as a rule, at the time period when the shape and size of the Purkinje cell body became close to the definitive ones, and their vertical and horizontal diameters reached the values characteristic of adult animals.     

The number of active Purkinje cells in the microelectrod track as an indicator of maturity of the cerebellum motor function in mature- and immature-born animals

In experiments on 5 age groups of anesthetized guinea pigs (from newborns to 4 weeks of postnatal ontogenesis), activity of cerebellum Purkinje cells (PC) (IV–VII lobules of cerebellar vermis) was studied in the single track of microelectrode passing through cell layers. It has been shown that as early as several hours after birth, in the superficial layer of cerebellar cortex, there are recorded occasional background-active, but functionally mature PC in the form of simple and complex spikes and accordingly reflecting synaptic PC activation by afferent inputs of mossy and climbing fibers. The functional manifestation of the guinea pig motor behavior at this period of ontogenesis is act of their standing. At this period of ontogenesis, in the newborn and one-day old guinea pigs, on average, from 1 to rarely 11 active PC are recorded in the single microelectrode track. At the one-week age, the highest number of active PC in the track somewhat increases, predominantly at the expense of the mean from the total number of cells in the track. In the 2-week old guinea pigs the mean number of active PC in the track somewhat falls, while in the 4-week old and adult animals it again exceeds, although slightly, the maximal number of PC in the track of newborn animals. The relatively high number of active PC at the very initial period of postnatal ontogenesis can indicate importance of motor function in the congenital food-procuring reflex.     

A role for the cerebellum in the control of limb movement velocity

Accepting, rejecting or modifying the many different theories of the cerebellum's role in the control of movement requires an understanding of the signals encoded in the discharge of cerebellar neurons and how those signals are transformed by the cerebellar circuitry. Particularly challenging is understanding the sensory and motor signals carried by the two types of action potentials generated by cerebellar Purkinje cells, the simple spikes and complex spikes. Advances have been made in understanding this signal processing in the context of voluntary arm movements. Recent evidence suggests that mossy fiber afferents to the cerebellar cortex are a source of kinematic signals, providing information about movement direction and speed. In turn, the simple spike discharge of Purkinje cells integrates this mossy fiber information to generate a movement velocity signal. Complex spikes may signal errors in movement velocity. It is proposed that the cerebellum uses the signals carried by the simple and complex spike discharges to control movement velocity for both step and tracking arm movements.     

Cerebellar LTD and pattern recognition by Purkinje cells

Many theories of cerebellar function assume that long-term depression (LTD) of parallel fiber (PF) synapses enables Purkinje cells to learn to recognize PF activity patterns. We have studied the LTD-based recognition of PF patterns in a biophysically realistic Purkinje-cell model. With simple-spike firing as observed in vivo, the presentation of a pattern resulted in a burst of spikes followed by a pause. Surprisingly, the best criterion to distinguish learned patterns was the duration of this pause. Moreover, our simulations predicted that learned patterns elicited shorter pauses, thus increasing Purkinje-cell output. We tested this prediction in Purkinje-cell recordings both in vitro and in vivo. In vitro, we found a shortening of pauses when decreasing the number of active PFs or after inducing LTD. In vivo, we observed longer pauses in LTD-deficient mice. Our results suggest a novel form of neural coding in the cerebellar cortex.     

Cerebellar complex spikes multiplex complementary behavioral information

Purkinje cell (PC) discharge, the only output of cerebellar cortex, involves 2 types of action potentials, high-frequency simple spikes (SSs) and low-frequency complex spikes (CSs). While there is consensus that SSs convey information needed to optimize movement kinematics, the function of CSs, determined by the PC’s climbing fiber input, remains controversial. While initially thought to be specialized in reporting information on motor error for the subsequent amendment of behavior, CSs seem to contribute to other aspects of motor behavior as well. When faced with the bewildering diversity of findings and views unraveled by highly specific tasks, one may wonder if there is just one true function with all the other attributions wrong? Or is the diversity of findings a reflection of distinct pools of PCs, each processing specific streams of information conveyed by climbing fibers? With these questions in mind, we recorded CSs from the monkey oculomotor vermis deploying a repetitive saccade task that entailed sizable motor errors as well as small amplitude saccades, correcting them. We demonstrate that, in addition to carrying error-related information, CSs carry information on the metrics of both primary and small corrective saccades in a time-specific manner, with changes in CS firing probability coupled with changes in CS duration. Furthermore, we also found CS activity that seemed to predict the upcoming events. Hence PCs receive a multiplexed climbing fiber input that merges complementary streams of information on the behavior, separable by the recipient PC because they are staggered in time.

Purkinje cell (PC) discharge, the only output of cerebellar cortex, involves both high-frequency simple spikes and low-frequency complex spikes; the function of the latter, determined by a PC’s climbing fibre input, remains controversial. This study shows that PCs receive a multiplexed climbing fibre input that merges complementary streams of information relevant for behaviour.     

Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.     

Postnatal development of the cerebellar Purkinje cell shape in guinea pig ontogenesis

In sagittal cerebellum sections, morphometrical study of cerebellum of mature-born animals - guinea pigs - was performed using Nissl's procedure. A change of shape and volume of Purkinje cells and their nuclei in the course of the guinea pig postnatal ontogenesis was studied. It has been shown that both the growth process itself and the rate of formation of the definite form of Purkinje cells and of their nuclei in the course of ontogenesis proceeds non-uniformly. The most intensive growth of vertical and horizontal diameters of Purkinje cells and of their nuclei is observed during the 1st and 4th weeks of postnatal life. Especially rapid is an increase of horizontal diameters of Purkinje cells and of their nuclei, which impairs the ovoid-bear-like shape to the cerebellar Purkinje cells of adult guinea pigs.     

Postnatal development of the shape of cerebellar Purkinje cells in guinea pig ontogenesis

In sagittal cerebellum sections, morphometrical study of cerebellum of mature-born animals—guinea pigs—was performed using Nissl’s procedure. A change of shape and volume of Purkinje cells and their nuclei in the course of the guinea pig postnatal ontogenesis was studied. It has been shown that both the growth process itself and the rate of formation of the definite form of Purkinje cells and of their nuclei in the course of ontogenesis proceeds non-uniformly. The most intensive growth of vertical and horizontal diameters of Purkinje cells and of their nuclei is observed during the 1st and 4th weeks of postnatal life. Especially rapid is an increase of horizontal diameters of Purkinje cells and of their nuclei, which impairs the ovoid-bear-like shape to the cerebellar Purkinje cells of adult guinea pigs.     

Effect of harmaline on firing pattern of rat cerebellar Purkinje cells in ontogenesis

In this work, responses of rat Purkinje cells to intraperitoneal administration of the hallucinogenic alkaloid harmaline (0.15 mg/kg) were studied in the course of ontogenesis. The experiments were carried out on Wistar rats of three age groups: rat pups (13–18 days), adult animals (2–7 months), and aged rats (25–36 months). In Purkinje cell firings, two types of electric reactions were revealed; they were similar in all age group of the animals. In cells with the 1st type of reactions, in response to the harmaline administration there was recorded a significant increase of frequency of complex spikes, accompanied by disappearance of simple spikes. In the activity of Purkinje cells of the 2nd type, the complex spike frequency also increased; however, the firing simple spikes were preserved, although with a decrease of their frequency as compared with norm. Essential changes of activity of the cerebellar Purkinje cells were found in the rat pups and aged animals in comparison with adult rats, which agrees well with immaturity of various cerebellar structures in the first case and with involutionary changes in the second case.     

Effect of harmaline on firing pattern of rat cerebellar Purkinje cells in ontogenesis

In this work, responses of rat Purkinje cells to intraperitoneal administration of the hallucinogenic alkaloid harmaline (0.15 mg/kg) were studied in the course of ontogenesis. The experiments were carried out on Wistar rats of three age groups: rat pups (13-18 days), adult animals (2-7 months), and aged rats (25-36 months). In Purkinje cell firings, two types of electric reactions were revealed; they were similar in all age group of the animals. In cells with the 1st type of reactions, in response to the harmaline administration there was recorded a significant increase of frequency of complex spikes, accompanied by disappearance of simple spikes. In the activity of Purkinje cells of the 2nd type, the complex spike frequency also increased; however, the firing simple spikes were preserved, although with a decrease of their frequency as compared with norm. Essential changes of activity of the cerebellar Purkinje cells were found in the rat pups and aged animals in comparison with adult rats, which agrees well with immaturity of various cerebellar structures in the first case and with involutionary changes in the second case.     

Signal processing in cerebellar Purkinje cells

Mechanisms and functional implications of signal processing in cerebellar Purkinje cells have been the subject of recent extensive investigations. Complex patterns of their planar dendritic arbor are analysed with computer-aided reconstructions and also topological analyses. Local computation may occur in Purkinje cell dendrites, but its extent is not clear at present. Synaptic transmission and electrical and ionic activity of Purkinje cell membrane have been revealed in detail, and related biochemical processes are being uncovered. A special type of synaptic plasticity is present in Purkinje cell dendrites; long-term depression (LTD) occurs in parallel fiber-Purkinje cell transmission when the parallel fibers are activated with a climbing fiber innervating that Purkinje cell. Evidence indicates that synaptic plasticity in Purkinje cells is due to sustained desensitization of Purkinje dendritic receptors to glutamate, which is a putative neurotransmitter of parallel fibers, and that conjunctive activation of a climbing fiber and parallel fibers leads to desensitization through enhanced intradendritic calcium concentration. A microzone of the cerebellar cortex is connected to an extracerebellar neural system through the inhibitory projection of Purkinje cells to a cerebellar or vestibular nuclear cell group. Climbing fiber afferents convey signals representing control errors in the performance of a neural system, and evoke complex spikes in Purkinje cells of the microzone connected to the neural system. Complex spikes would modify the performance of the microzone by producing LTD in parallel fiber-Purkinje cell synapses, and consequently would improve the overall performance of the neural system. The primary function of the cerebellum thus appears to be endowing adaptability to numerous neural control systems in the brain and spinal cord through error-triggered reorganization of the cerebellar cortical circuitry.     

电刺激大鼠巨细胞网状核对小脑浦肯野细胞自发和诱发电活动的影响

本研究在麻醉并制动的大鼠上观察了电刺激巨细胞网状核(Gi)对小脑浦肯野细胞(PC)自发及诱发简单锋电位的影响。结果如下:(1)刺激Gi可使PC的简单锋电位出现潜伏期小于20ms的抑制性或兴奋性反应,并以抑制性反应为主。抑制性反应持续40-100ms,而兴奋性反应的时程可达200ms以上;(2)注射5-HT_2型受体阻断剂methysergide可以减弱或阻断电刺激Gi对PC自发简单锋电位的抑制作用;(3)条件性Gi刺激可以显著压抑或加强由刺激对侧大脑皮层感觉运动区引起的PC诱发简单锋电位反应。以上结果说明:在大鼠存在Gi-小脑通路,这一通路中的部分纤维是5-HT能的。Gi-小脑纤维可能通过突触和/或非经典突触的化学传递方式对PC的电活动产生某种调制性的影响。推测Gi-小脑传入纤维投射可能在某些小脑功能活动,如肌紧张及姿势的调节等方面发挥重要作用。     

Dependence of different spike sequences on the mean neuronal firing rate in the neocortex in vivo and in vitro

Neuronal spikes were recorded extracellularly in rabbit visual cortex in vivo (88 cells) and in surviving slices of guinea pig sensorimotor cortex in vitro (50 cells). Spike sequences (SS) with monotonically increasing (SS+) and decreasing (SS-) interspike intervals were detected. Relative number of spikes of SS in the recording was closely associated with SS generation. The relative number of spikes was plotted against the average firing rate, this function had a biphasic character with the critical point around 7 Hz. The rate of change in interspike duration (the slope) was virtually independent of the firing rate, but was significantly different in vivo and in vitro conditions for both SS+ (325 and 180 ms/s, respectively) and SS- (270 and 160 ms/s, respectively). By and large, in vivo and in vitro the spike sequence parameters depended in the average firing rate in the same manner. The role of the spike sequences in rhythmic and information processes in neocortex is discussed.     

Visualization of IP(3) dynamics reveals a novel AMPA receptor-triggered IP(3) production pathway mediated by voltage-dependent Ca(2+) influx in Purkinje cells

IP(3) signaling in Purkinje cells is involved in the regulation of cell functions including LTD. We have used a GFP-tagged pleckstrin homology domain to visualize IP(3) dynamics in Purkinje cells. Surprisingly, IP(3) production was observed in response not only to mGluR activation, but also to AMPA receptor activation in Purkinje cells in culture. AMPA-induced IP(3) production was mediated by depolarization-induced Ca(2+) influx because it was mimicked by depolarization and was blocked by inhibition of the P-type Ca(2+) channel. Furthermore, trains of complex spikes, elicited by climbing fiber stimulation (1 Hz), induced IP(3) production in Purkinje cells in cerebellar slices. These results revealed a novel IP(3) signaling pathway in Purkinje cells that can be elicited by synaptic inputs from climbing fibers.     

Zonal distribution of Purkinje cells in the zebrafish cerebellum: analysis by means of a specific monoclonal antibody

We have isolated a monoclonal antibody that recognizes a 42-kDa protein from adult zebrafish brain. The antibody stains the typical drop-shaped perikaryon of Purkinje cells and their dendrites. The cerebellum of teleosts has complex features. It is composed of three parts; the valvula cerebelli (Va), the corpus cerebelli (CCe), and the crista cerebellaris (CC). In higher vertebrates, the molecular layer is always found as the most outer layer of the cerebellum, but in teleosts, some of the granular cells are located on the surface of the Va. In higher vertebrates, the boundary between the granular and molecular layers always contains Purkinje cells, but this does not occur in teleosts. The Purkinje cells are found only in a part of the boundary in Va. We have found that the layer containing Purkinje cells forms a continuous zone in the cerebellum in the zebrafish. The complex structure of the cerebellum is more easily understood with the aid of the concept of a "Purkinje zone". The Purkinje zone starts at the caudal end of Val (lateral division of Va), turns at the edge of Va toward Vam (medial division of Va), connects to CCe, and ends at the bottom of CCe. The dendrites are found only on one side of the zone. The dendrites of the Purkinje cells in Vam are planar and are packed regularly, similar to those of higher vertebrates. However, the dendrites in Val and the posterior part of CCe are not planar and are irregularly packed.