Connections of the Lateral Reticular Nucleus to the Lateral Vestibular Nucleus in the Rat. An Anterograde Tracing Study with Phaseolus vulgaris Leucoagglutinin

Efferent projections from the lateral reticular nucleus in the rat were investigated with anterograde transport of Phaseolus vulgaris leucoagglutinin. Besides the well known mossy fibre connections to the cerebellar cortex and collaterals to the cerebellar nuclei, a substantial bilateral projection to the lateral vestibular nucleus was found. Terminal arborizations found within this nucleus appeared to detach from the reticulocerebellar fibres in the cerebellar white matter and enter the lateral vestibular nucleus from dorsally. This projection may have functional relevance for the control, by ascending spinal pathways, of the descending lateral vestibulospinal tract.     

Entopeduncular Nucleus Projections to the Lateral Habenula Contribute to Cocaine Avoidance

The aversive properties associated with drugs of abuse influence both the development of addiction and relapse. Cocaine produces strong aversive effects after rewarding effects wear off, accompanied by increased firing in the lateral habenula (LHb) that contributes to downstream activation of the rostromedial tegmental nucleus (RMTg). However, the sources of this LHb activation are unknown, as the LHb receives many excitatory inputs whose contributions to cocaine aversion remain uncharacterized. Using cFos activation and in vivo electrophysiology in male rats, we demonstrated that the rostral entopeduncular nucleus (rEPN) was the most responsive region to cocaine among LHb afferents examined and that single cocaine infusions induced biphasic responses in rEPN neurons, with inhibition during cocaine''s initial rewarding phase transitioning to excitation during cocaine''s delayed aversive phase. Furthermore, rEPN lesions reduced cocaine-induced cFos activation by 2-fold in the LHb and by a smaller proportion in the RMTg, while inactivation of the rEPN or the rEPN-LHb pathway attenuated cocaine avoidance behaviors measured by an operant runway task and by conditioned place aversion (CPA). These data show an essential but not exclusive role of rEPN and its projections to the LHb in processing the aversive effects of cocaine, which could serve as a novel target for addiction vulnerability.SIGNIFICANCE STATEMENT Cocaine produces well-known rewarding effects but also strong aversive effects that influence addiction propensity, but whose mechanisms are poorly understood. We had previously reported that the lateral habenula (LHb) is activated by cocaine and contributes to cocaine''s aversive effects, and the current findings show that the rostral entopeduncular nucleus (rEPN) is a major contributor to this LHb activation and to conditioned avoidance of cocaine. These findings show a critical, though not exclusive, rEPN role in cocaine''s aversive effects, and shed light on the development of addiction.     

Organization of the Visual Reticular Thalamic Nucleus of the Rat

The visual sector of the reticular thalamic nucleus has come under some intense scrutiny over recent years, principally because of the key role that the nucleus plays in the processing of visual information. Despite this scrutiny, we know very little of how the connections between the reticular nucleus and the different areas of visual cortex and the different visual dorsal thalamic nuclei are organized. This study examines the patterns of reticular connections with the visual cortex and the dorsal thalamus in the rat, a species where the visual pathways have been well documented. Biotinylated dextran, an anterograde and retrograde tracer, was injected into different visual cortical areas [17; rostral 18a: presumed area AL (anterolateral); caudal 18a: presumed area LM (lateromedial); rostral 18b: presumed area AM (anteromedial); caudal 18b: presumed area PM (posteromedial)] and into the different visual dorsal thalamic nuclei (posterior thalamic, lateral posterior, lateral geniculate nuclei), and the patterns of anterograde and retrograde labelling in the reticular nucleus were examined. From the cortical injections, we find that the visual sector of the reticular nucleus is divided into subsectors that each receive an input from a distinct visual cortical area, with little or no overlap. Further, the resulting pattern of cortical terminations in the reticular nucleus reflects largely the patterns of termination in the dorsal thalamus. That is, each cortical area projects to a largely distinct subsector of the reticular nucleus, as it does to a largely distinct dorsal thalamic nucleus. As with each of the visual cortical areas, each of the visual dorsal thalamic (lateral geniculate, lateral posterior, posterior thalamic) nuclei relate to a separate territory of the reticular nucleus, with little or no overlap. Each of these dorsal thalamic territories within the reticular nucleus receives inputs from one or more of the visual cortical areas. For instance, the region of the reticular nucleus that is labelled after an injection into the lateral geniculate nucleus encompasses the reticular regions which receive afferents from cortical areas 17, rostral 18b and caudal 18b. These results suggest that individual cortical areas may influence the activity of different dorsal thalamic nuclei through their reticular connections.     

The Organization of Projections from Subdivisions of the Auditory Cortex and Thalamus to the Auditory Sector of the Thalamic Reticular Nucleus in Galago

Anterograde and retrograde transport techniques were used to study the connexions between different subdivisions of the auditory cortex and thalamus with the thalamic reticular nucleus in the prosimian, Galago. In particular, the goal was to determine whether the primary auditory nucleus, GMv, and its cortical target, area I of the auditory cortex (A I), project to a different region of the auditory sector of the reticular nucleus from the secondary auditory nuclei, GMmc and Po and their cortical targets outside A I. The results show that the projections to and from the auditory sector are indeed segregated: injections of wheatgerm agglutinin-conjugated horseradish peroxidase into either GMmc or Po labelled cells and terminals along the medial, lateral and ventral borders of the auditory sector, forming a U-shaped pattern. Projections from area II of the auditory cortex produced almost an identical pattern of the terminal labelling in the auditory sector. In contrast, injections into GMv-labelled cells and terminals in the centre region of the auditory sector, in the 'interior' of the U-shaped region. Projections from A I were distributed to both the U-shaped border region and the central core of the auditory sector probably because A I received projections from GMmc, Po and GMv. The significance of these results depends on a comparison between the auditory and visual sectors of the reticular nucleus. Both sectors are divided into tiers or subsectors-one related to the primary relay nucleus, i.e. GLd or GMv, and the other related to the secondary relay nuclei, i.e. pulvinar nucleus, GMmc, Po, etc.     

Compartmentalization of the Deep Cerebellar Nuclei Based on Afferent Projections and Aldolase C Expression

The distribution of aldolase C (zebrin II)-positive and -negative Purkinje cells (PCs) can be used to define about 20 longitudinally extended compartments in the cerebellar cortex of the rat, which may correspond to certain aspects of cerebellar functional localization. An equivalent compartmental organization may exist in the deep cerebellar nuclei (DCN). This DCN compartmentalization is primarily represented by the afferent projection pattern in the DCN. PC projections and collateral nuclear projections of olivocerebellar climbing fiber axons have a relatively localized terminal arbor in the DCN. Projections of these axons make a closed olivo-cortico-nuclear circuit to connect a longitudinal stripe-shaped cortical compartment to a small subarea in the DCN, which can be defined as a DCN compartment. The actual DCN compartmentalization, which has been revealed by systematically mapping these projections, is quite different from the cortical compartmentalization. The stripe-shaped alternation of aldolase C-positive and -negative narrow longitudinal compartments in the cerebellar cortex is transformed to the separate clustering of positive and negative compartments in the caudoventral and rostrodorsal DCN, respectively. The distinctive projection of aldolase C-positive and -negative PCs to the caudoventral and rostrodorsal DCN underlies this transformation. Accordingly, the medial cerebellar nucleus is divided into the rostrodorsal aldolase C-negative and caudoventral aldolase C-positive parts. The anterior and posterior interposed nuclei generally correspond to the aldolase C-negative and -positive parts, respectively. DCN compartmentalization is important for understanding functional localization in the DCN since it is speculated that aldolase C-positive and -negative compartments are generally associated with somatosensory and other functions, respectively.     

The functional anatomy of the cerebrocerebellar circuit: A review and new concepts

The cerebrocerebellar circuit is a feedback circuit that bidirectionally connects the neocortex and the cerebellum. According to the classic view, the cerebrocerebellar circuit is specifically involved in the functional regulation of the motor areas of the neocortex. In recent years, studies carried out in experimental animals by morphological and physiological methods, and in humans by magnetic resonance imaging, have indicated that the cerebrocerebellar circuit is also involved in the functional regulation of the nonmotor areas of the neocortex, including the prefrontal, associative, sensory and limbic areas. Moreover, a second type of cerebrocerebellar circuit, bidirectionally connecting the hypothalamus and the cerebellum, has been detected, being specifically involved in the regulation of the hypothalamic functions. This review analyzes the morphological features of the centers and pathways of the cerebrocerebellar circuits, paying particular attention to their organization in different channels, which separately connect the cerebellum with the motor areas and nonmotor areas of the neocortex, and with the hypothalamus. Actually, a considerable amount of new data have led, and are leading, to profound changes on the views on the anatomy, physiology, and pathophysiology of the cerebrocerebellar circuits, so much they may be now considered to be essential for the functional regulation of many neocortex areas, perhaps all, as well as of the hypothalamus and of the limbic system. Accordingly, clinical studies have pointed out an involvement of the cerebrocerebellar circuits in the pathophysiology of an increasing number of neuropsychiatric disorders.     

Organization of the Visual Sector of the Thalamic Reticular Nucleus in Galago

Projections to and from the visual sector of the thalamic reticular nucleus were studied in the prosimian primate genus Galago by anterograde and retrograde transport of WGA-HRP injected into the dorsal lateral geniculate nucleus (GLd), pulvinar nucleus, and their cortical targets. Contrary to the idea that thalamic connections with the reticular nucleus are not delimited sharply between nuclei associated with the same modality, our results show a distinct laminar segregation of the projections from the GLd and pulvinar nuclei. The GLd is connected reciprocally with the lateral {frsol|2/3} of the caudal part of the reticular nucleus, and the striate cortex sends projections to the same lateral tier. Both sets of projections are organized topographically, lines of projection taking the form of slender elongated strips that run from caudo-dorsal to rostro-ventral within the nucleus. The pulvinar nucleus, which projects to several areas of the temporal, parietal, and occipital lobes, including the striate cortex, is connected reciprocally with the medial {frsol|1/3} of the caudal part of the reticular nucleus. Every injection into the pulvinar nucleus labelled a wide area of the medial tier, with no indication of visuotopic organization. The projections from the middle temporal area, one of the principal targets of the pulvinar nucleus, also terminate only in the medial tier of the visual sector. And we would expect that, in general, a thalamic nucleus and its cortical target would project to the same part of the reticular nucleus. The case of the striate area is an exception but only in the sense that it projects to the pulvinar nucleus as well as GLd. Thus an injection into a single locus in area 17 produces two parallel strips in the visual sector of the reticular nucleus, but both are in the lateral tier. We propose that each strip arises from a separate population of cells with cortical layer VI, one with an allegiance to the GLd and the other to the pulvinar nucleus.     

Cytology and intrinsic organization of the perihypoglossal nuclei in the cat

The morphology of the neurons in the perihypoglossal nuclei (nucleus prepositus, nucleus intercalatus, and nucleus of Roller) of the cat was studied in normal Nissl material, and by intracellular injection of horseradish peroxidase. The neurons in the nucleus prepositus were morphologically heterogeneous. Many of the cells in the ventromedial part of the caudal prepositus had relatively large somata, and complex dendritic trees which arose from numerous proximal dendrites and ramified extensively in the ventromedial aspect of the prepositus. These neurons had thick axons which typically did not give rise to local collaterals. The cells in the dorsolateral part of the caudal prepositus tended to have small somata, and dendritic trees which arborized in that region of the nucleus. The axons of these small cells frequently gave rise to local collaterals which terminated in the prepositus. Most of the cells in the prepositus had medium-sized somata and relatively few dendrites which branched in an isodendritic manner and extended for long distances, frequently leaving the nucleus. These "principal" prepositus neurons had axons which arborized unilaterally, and often gave rise to collaterals which terminated in either the ipsilateral or contralateral prepositus. The neurons in the nucleus of Roller and nucleus intercalatus which were intracellularly injected with horseradish peroxidase resembled the multidendritic and small prepositus cells, respectively. The intrinsic connectivity of the perihypoglossal nuclei was also studied by injecting horseradish peroxidase or 3H-leucine into the prepositus nucleus. The results of these experiments suggest that the perihypoglossal nuclei are highly interconnected bilaterally, although the large cells in the ventromedial prepositus and the nucleus of Roller contribute little to these intrinsic connections, and are not major recipients of intrinsic inputs. On the other hand, the magnitude of the reciprocal connections between the prepositus and the nucleus intercalatus suggests that they are functionally related.     

Terminal Degeneration in the Lateral Septum of the Rat after Suprachiasmatic Nucleus Lesion

Abstract: Nerve terminals in the lateral septum were studied by electron microscopy in the rat after lesions of the suprachiasmatic nuclei (SCN). The results were as follows: 1) The electron-lucent degenerations showed a reduction in the number of vesicles and the swelling of terminals and/or vesicles. These degenerating terminals predominated at two days of survival period. The electron-dense degenerations which showed a darkening and shrinkage of the terminals mainly appeared at four days of survival period. 2) Most of the degenerating terminals contained large core vesicles of a diameter in the range of 800–1500 A. 3) The percentage of the degenerating terminals to all the terminals on the electron micrographs was about 7%. 4) The F-type synapses were not found in the lateral septum of the normal and SCN lesion rats. These data confirmed the existence of the projection which reached the lateral septum from the SCN and suggested to us that these synapses were so-called peptidergic synapses.     

Effect of Complete and Partial Bilateral Lesions of the Deep Cerebellar Nuclei on Amygdaloid Kindling in Rats

Summary: Purpose: The roles of the deep cerebellar nuclei in epileptogenesis and seizure expression are not well defined. To determine their properties, we examined the effects of lesions to the dentate, fastigial, and interpositus nuclei in adult rats that were electrically kindled in the amygdaloid complex. Changes in afterdischarge duration (ADD) as well as the expression and progression of behavioral seizures to fully generalized tonic-clonic convulsions (stage 5) were assessed.
Methods: Fifty rats first underwent bilateral electrolytic lesions of either the dentate, fastigial, or interpositus nuclei. After a 7–day recovery period, they were kindled daily until they manifested two stage 5 convulsions. Careful histological examination was used to determine lesion extent.
Results: When the dentate or fastigial nucleus was completely destroyed on the side contralateral to the stimulated amygdala, fewer stimulations were required to produce stage 5 seizures and latencies to the expression of forelimb clonus were shorter, as were ADD. On the other hand, when the dentate or fastigial neucleus was only partly obliterated on the contralateral side, more stimulations were required to produce stage 5 seizures and ADD was longer. Neither complete nor partial lesions of the interpositus nuclei had any effect on the number of stimulations to reach a stage 5 seizure, latency to the expression of clonus, or ADD.
Conclusions: Our findings suggest that the dentate and fastigial nuclei, but not the interpositus nuclei, may normally retard epileptogenesis and inhibit clonic behaviors, but paradoxically may facilitate ADD.     

Postsynaptic Targets of Purkinje Cell Terminals in the Cerebellar and Vestibular Nuclei of the Rat

The cerebellar and vestibular nuclei consist of a heterogeneous group of inhibitory and excitatory neurons. A major proportion of the inhibitory neurons provides a GABAergic feedback to the inferior olive, while the excitatory neurons exert more direct effects on motor control via non-olivary structures. At present it is not clear whether Purkinje cells innervate all types of neurons in the cerebellar and vestibular nuclei or whether an individual Purkinje cell axon can innervate different types of neurons. In the present study, we studied the postsynaptic targets of Purkinje cell axons in the rat using a combination of pre-embedding immunolabelling of the Purkinje cell terminals by L7, a Purkinje cell-specific marker, and postembedding GABA and glycine immunocytochemistry. In the cerebellar nuclei, vestibular nuclei and nucleus prepositus hypoglossi Purkinje cell terminals were found apposed to GABAergic and glycinergic neurons as well as to larger non-GABAergic, non-glycinergic neurons. In the cerebellar and vestibular nuclei individual Purkinje cell terminals innervated both the inhibitory and excitatory neurons. Both types of neurons were contacted not only by GABAergic Purkinje cell terminals but also by GABA-containing terminals that were not labelled for L7 and by non-GABAergic, non-glycinergic terminals that formed excitatory synapses. Glycine-containing terminals were relatively scarce (<2% of the GABA-containing terminals) and frequently contacted the larger non-GABAergic, non-glycinergic neurons. To summarize, Purkinje cell axons evoke their effects through different types of neurons present in the cerebellar and vestibular nuclear complex. The observation that individual Purkinje cells can innervate both excitatory and inhibitory neurons suggests that the excitatory cerebellar output system and the inhibitory feedback to the inferior olive are controlled simultaneously.     

Electrical Stimulation of Specific Brainstem Nuclei Suppresses Growth Hormone-Releasing Hormone-Induced Growth Hormone Secretion in the Pentobarbital Anaesthetized Rat

To clarify the neural mechanism related to suppression of growth hormone (GH) secretion, biphasic electrical stimulation was delivered into several brainstem nuclei in the pentobarbital anaesthetized rat. A concentric bipolar stimulating electrode was implanted chronically one week prior to the electrical stimulation. Ninety min before the electrical stimulation, the rats were anaesthetized by ip injection of pentobarbital and a silastic cannula was inserted into the right atrium for blood sampling. Blood samples were withdrawn five times (0, 10, 20, 30 and 60 min) during the experiment. Electrical stimulation was delivered for 10 min just after the first blood sampling. One min after the onset of the stimulation, human GH-releasing hormone was injected iv to induce GH secretion. Electrical stimulation of several brainstem nuclei, i.e. the locus coeruleus, the rostral portion of the nucleus tractus solitarius and the lateral reticular nucleus suppressed GH secretion and the central gray of the pons showed a tendency for the suppression of GH secretion. On the other hand, electrical stimulation of the parabrachial nucleus and the caudal portion of the nucleus tractus solitarius did not suppress GH secretion. These suppressions were nullified by prior electrolytic lesioning of the hypothalamic periventricular nucleus where the major cell bodies of somatostatin immunoreactive fibres in the median eminence originate. These results indicate that electrical stimulation of several brainstem nuclei excites somatostatin neurons in the periventricular nucleus which are responsible for the suppression of GH secretion.     

Functional Classification of Neurons in the Mouse Lateral Cerebellar Nuclei

The deep cerebellar nuclei (DCN) are at the center of the cerebellum not only anatomically but also functionally. Classical anatomical studies have described different types of DCN neurons according to their expression of various marker proteins, but only recently have we begun to characterize these different cell types according to their electrophysiological properties. These efforts have benefited greatly from the availability of transgenic mouse lines that express green fluorescent protein under the control of the glutamic acid decarboxylase (GAD67) and glycine transporter (GlyT2) promoters, which are markers for GABAergic and glycinergic neurons, respectively. These studies have identified several types of neurons within the lateral cerebellar nuclei, each of which exhibits distinct active membrane properties. In addition to their differential use of neurotransmitters (glutamate, GABA, or glycine), these cell types also receive and provide synaptic information from different sources and to different targets.     

Development of the Thalamic Reticular Nucleus in Ferrets with Special Reference to the Perigeniculate and Perireticular Cell Groups

This study describes the development of the ferret thalamic reticular nucleus from Nissl-stained and from parvalbumin-immunostained sections. From early stages [embryonic day (E) 23-E25], there is a large group of ventral thalamic cells which lies between the dorsal thalamus and the primordial internal capsule. This group of cells, the primordial reticular nucleus, gives rise to the main body of the reticular nucleus, the perigeniculate nucleus and the perireticular nucleus. In the reticular nucleus, there are two waves of parvalbumin expression during development. The first wave begins prenatally in small cells which are seen rarely after birth. Their fate is not clear: they may have lost immunoreactivity, migrated elsewhere, or died. At the end of the first wave, a second wave begins in a distinct group of larger ovoid reticular cells, which appear to remain into adulthood. At about birth, the dorsocaudal pole of the reticular nucleus first forms the perigeniculate nucleus. During this developmental stage, cells which make up the reticular and perigeniculate nuclei are the only parvalbumin-immunostained structures in the thalamus. Thus, rather than develop from the dorsal thalamus, the perigeniculate nucleus seems to have its origins in the ventral thalamus together with the reticular nucleus. During development, the reticular nucleus is associated closely with a large mass of cells located in the internal capsule, called the perireticular nucleus. Later, the perireticular nucleus is dramatically reduced in size: that is, there is a large reduction in the number of perireticular cells seen per section and in the extent of the nucleus across the internal capsule. There are two cytoarchitectonically distinct groups of perireticular cells. One group of cells, called the large-celled perireticular zone (LPR), enters the internal capsule from early prenatal development (E25). Many of these cells reach the globus pallidus and extend as far as the cortical subplate zone. The LPR together with the subplate form an extensive neuronal network in the white matter during early development, which disappears later in development (about postnatal day 20). The second group of perireticular cells is made up of smaller cells and is called the small-celled perireticular zone (SPR). These small cells enter the internal capsule from the reticular nucleus just prior to birth. Many of the cells in the SPR remain in the adult.     

Evidence That the Lateral Geniculate Nucleus Regulates the Normal Development of Visual Corticocortical Projections in the Cat

The aim of this work was to examine the influence of subcortical afferents on the development of corticocortical projections in the cat's visual cortex. In the adult, corticocortical axons project with precision to link retinotopically corresponding points in visual areas 17 and 18. In the newborn kitten, an excess of corticocortical connections is generated, leading to a degree of imprecision in the early pathways. During the first postnatal month, the loss of some of these early connections lowers their densities and increases the accuracy with which they project. These processes occur in an environment already influenced by afferents from the lateral geniculate nucleus and we tested the extent to which these existing inputs are required for corticocortical development. We lesioned the lateral geniculate nucleus with ibotenic acid in newborn kittens and studied connections from area 17 to area 18, and vice versa, after 1 month. In lesioned kittens, there were fewer corticocortical projections than normal in these reciprocal pathways and those that were present retained an immature, widespread pattern of projection. These results suggest that geniculate afferents are crucial for generating sufficient numbers of corticocortical projections and for creating the precision in their mapping.     

Purkinje Cell Input to Cerebellar Nuclei in Tottering: Ultrastructure and Physiology

Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei. Freek E. Hoebeek and Sara Khosrovani contributed equally.     

Involvement of Precerebellar Nuclei in Pick''s Disease

Pick's disease is a progressive degenerative disorder of the human brain which involves not only numerous areas of the cerebral cortex but also a characteristic set of subcortical nuclei. The disorder is associated with the formation of abnormal and hyperphosphorylated tau protein, which occurs in only a few susceptible neuronal types and leads to major cytoskeletal alterations. Preferentially affected by the destructive process are small nerve cells of both cortical areas and subcortical nuclei. Immunoreactions for abnormally phosphorylated tau protein permit identification of the alterations in their entirety. In an initial step in their development, patches of a nonargyrophilic material appear, irregularly filling both the somata and neurites of afflicted cells. The abnormal material is then partially converted into condensed spindle-shaped or spherical structures, which gradually become significantly argyrophilic. Globose argyrophilic Pick bodies eventually appear within the somata, and small Pick neurites of variable sizes and shapes develop in varicose expansions of the dendritic processes. Silver staining reveals only a fraction of the abnormal material and is adequate only for diagnostic purposes, while immunostaining of the abnormal tau protein discloses the complete neuropathological picture. The present study points to a conspicuous affliction of specific precerebellar nuclei in Pick's disease. Immunoreactive punctae, probably corresponding to terminal synaptic boutons of afferent fibers, appear at sites in the inferior olive receiving intense input from the cerebral cortex. The brunt of the changes, however, are borne by the pontine gray, the arcuate nucleus, the pontobulbar body, and the paramedian reticular nucleus. Altered areas show immunoreactive punctae and an abundance of small immunoreactive nerve cells partially containing Pick bodies and Pick neurites. Again, a feature common to all the affected nuclei is that they receive major input from the cerebral cortex, while other precerebellar nuclei with preponderant input from the spinal cord and/or other noncortical sources remain unscathed or exhibit only sparse involvement. The lesional pattern which develops in specific precerebellar nuclei is interpreted to be a partial reflection of the cortical involvement of Pick's disease.     

The Role of SK Calcium-Dependent Potassium Currents in Regulating the Activity of Deep Cerebellar Nucleus Neurons: A Dynamic Clamp Study

We used the method of dynamic current clamping to determine the properties and function of the SK calcium-dependent K⁺ current in neurons of the deep cerebellar nuclei (DCN). As previously reported, block of SK current with apamin leads to bursting of DCN neurons and a steepening of the f-I curve. We show here that the properties of the slow spike afterhyperpolarization are fully controlled by SK current and we derive kinetic properties of this current that explain its action on DCN neurons. Overall, the SK current provides an effective mechanism to tune the regularity of spiking and the f-I curve of DCN neurons.