Heinrich Bantli

Anatomical and physiological evidence for a cerebellar nucleo-cortical projection in the cat

Combined neuroanatomical and electrophysiological experiments were performed to test the hypothesis that axon collaterals of neurons in the cerebellar nuclei project to the cerebellar cortex in cats. The anatomical studies demonstrated that (a) following the injection of tritiated leucine into the deep cerebellar nuclei, labeled fibers could be traced into the granular layer of the cerebellar cortex, and (b) following the injection of horseradish peroxidase into the cerebellar cortex, retrogradely labeled horseradish peroxidase-positive neurons were identified in the deep nuclei. The electrophysiological experiments confirmed the anatomical findings. Neurons in the dentate and interposed nuclei, identified by their antidromic activation from the brachium conjunctivum, could also be activated antidromically from the cerebellar surface. Collision experiments demonstrated that projections from the deep cerebellar nuclei to the cerebellar cortex are in part collaterals of efferent neurons projecting through the brachium conjunctivum. Care was taken to ensure that all recordings were obtained from the region of cell somata in order to minimize the likelihood of recording from neuronal elements passing through the cerebellar nuclei. These combined neuroanatomical and electrophysiological studies provide strong evidence supporting the existence of a collateral system from cerebellar output neurons to the cerebellar cortex. The existence of this collateral system emphasizes that the cerebellar cortex and cerebellar nuclei may comprise a functional unit in which these collaterals may serve as a substrate for feedback control of the cerebellar cortex by the cerebellar output.

Multiple branching of cerebellar efferent projections in cats

SummaryThe retrograde labeling of neurons in the deep cerebellar nuclei with horseradish peroxidase was used to compare the morphological characteristics of neurons in the dentate and interposed nuclei projecting in the cerebellothalamic, cerebello-olivary, and cerebellar nucleocortical pathways. The results from these studies demonstrated that cerebellothalamic and nucleocortical projections from the dentate and interposed nuclei originate from similar populations of spindle- and multipolar-shaped neurons with somal diameters throughout the range of cells present in the deep nuclei. However, only spindle-shaped neurons with somal diameters of 9–15 microns project in the cerebello-olivary pathway. From these anatomical studies, it was concluded that some of the neurons in the dentate and interposed nuclei which project to the thalamus, inferior olive, and cerebellar cortex have similar morphological characteristics. Electrophysiological experiments were carried out to investigate whether or not some of these neurons project to all three sites via axon collaterals. From stimulus sites in the thalamus, inferior olive, and cerebellar cortex, numerous neurons were antidromically activated in the cerebellar nuclei. Collision experiments between these antidromic responses confirmed that single neurons projected to all three of these sites. These studies therefore demonstrate that the axons of some neurons in the dentate and interposed nuclei have collateral branches in both the ascending and descending limbs of the brachium conjunctivum as well as in the cerebellar nucleocortical pathway. Functional implications of the collateral branching of cerebellar efferent projections are discussed.

The intracerebellar nucleocortical projection in a primate

SummaryExperiments were performed to determine if a nucleocortical system, a projection from the cerebellar nuclei to the cerebellar cortex, was present in primates. Both electrophysiological and neuroanatomical techniques were employed to investigate this question. It was shown that neurons within the dentate and interposed nuclei were antidromically activated by stimuli applied to the cerebellar cortex. In addition, cells in these nuclei were retrogradely labelled following injections of small amounts of horseradish peroxidase in the cerebellar cortex. The injection of tritiated leucine in the deep nuclei resulted in the labelling of fibers projecting from these structures to the cerebellar cortex which appeared to terminate within the granular layer. Additional electrophysiological studies showed that neurons projecting to the cerebellar cortex could also be antidromically activated from the ventrolateral thalamic nucleus, indicating that the nucleocortical projection in the primate arises at least in part as collaterals from neurons in the deep cerebellar nuclei which also project to extracerebellar structures, as was shown in the cat.

Monosynaptic activation of a direct reticulo-spinal pathway by the dentate nucleus

SummaryExperiments were performed to test the hypothesis that the output of the dentate nucleus can affect the excitability of spinal neurons via the reticular formation. In the first group of studies, the response of neurons in the medial reticular formation to stimulation of the dentate nucleus was investigated. In the second set of experiments, stimuli were applied in the same region of the medial reticular formation in order to determine whether neurons in the dentale nucleus could be antidromically activated from this part of the brainstem. The results indicate that the output from the dentate nucleus monosynaptically activates medial reticular neurons which project to the spinal cord. This finding, together with the observation that stimulation of the medial reticular formation can antidromically activate neurons in the dentate nucleus, demonstrates that there is an anatomical substrate by which the dentate nucleus can affect the excitability of spinal neurons via a rapidly conducting reticulospinal pathway.

Characteristics of the output from the dentate nucleus to spinal neurons via pathways which do not involve the primary sensorimotor cortex.

SummaryExperiments were performed to determine the action of the dentate output on neurons in the spinal cord mediated by pathways which do not involve the primary sensorimotor and premotor cortices. The dentate nucleus was electrically stimulated by stereotaxically placed electrodes in Rhesus monkeys whose contralateral sensorimotor and premotor cortices were ablated. The resultant changes in excitability of lumbar alpha motoneurons activated by Ia afferents from nerves innervating femoral, hamstring, gastrocnemius-soleus and peroneal muscles were measured by intracellular recordings and by determining the percent change in the amplitude of the monosynaptic reflex recorded from ventral roots. The effect of stimulation of the dentate nucleus on proprioceptive reflexes was determined by recording the changes in postsynaptic potentials evoked by selective stimulation of Ia and Ib afferent fibers. The results demonstrated that the dentate nucleus exerts a significant action on the excitability of spinal neurons via pathways which do not include the sensorimotor and premotor cortices. Whether the dentate stimulus produced an increase or decrease in the excitability of these neurons was dependent upon the site within the dentate nucleus at which the stimulus was applied, demonstrating that, in the decorticate preparation, the output from this nucleus is quite heterogeneous. In addition, stimulation of the dentate nucleus in these monkeys did not affect the Ia reflex pathway but significantly changed the amplitude of the inhibitory postsynaptic potential evoked by Ib afferents in lumbar alpha motoneurons.

An HRP and autoradiographic study of cerebellar corticonuclear-nucleocortical reciprocity in the monkey.

SummaryCombined injections of 3H-leucine and HRP were made into the monkey cerebellar cortex in order to identify any reciprocal connections between the corticonuclear and the nucleocortical pathways. These combined intraaxonal labeling experiments have demonstrated a considerable overlap of orthogradely labeled Purkinje cell axons and terminals with retrogradely labeled HRP-positive neurons in the ventrolateral region of the dentate nucleus following combined injections into the lateral hemisphere, and in the dorsal area of the dentate following combined injections into medial cortical areas of the anterior lobe. There were also areas within the deep cerebellar nuclei where orthogradely labeled corticonuclear terminals did not overlap with retrogradely labeled nucleocortical neurons.

Spinal input to the lateral cerebellum mediated by infratentorial structures

Abstract Recently, the output of the dentate nucleus has been shown to monosynaptically activate a reticulo-spinal pathway via the descending limb of the brachium conjunctivum. Since other regions of the cerebellum receive afferents from the structures to which they project, experiments were undertaken in both cats and monkeys to determine if the activation of ascending spinal pathways was capable of evoking responses in dentate neurons and the Purkinje cells of the neocerebellar cortex. The results demonstrated that both of these populations of neurons responded to electrical stimulation of spinal afferents from many regions of the body surface. Identical unitary responses and field potentials were evoked by stimulation of the spinal cord in decerebrate preparations. In addition, both types of responses were extremely sensitive to the administration of halothane or sodium pentobarbital, and they were not capable of following stimuli applied at frequencies of 10/s. These characteristics suggest that the responses to the activation of spinal pathways were evoked via an indirect spinoneocerebellar projection involving only infratentorial structures.

Effects of cerebellar stimulation on unitary activity within a chronic epileptic focus in a primate

Experiments were performed in unanesthetized awake monkeys to determine the effects of cerebellar stimulation on the activity of single cells within a chronic alumina cream seizure focus in the motor cortex. Six indices were used to characterize the epileptic and non-epileptic activity of the neurons within the focus. Cerebellar stimulation did not produce any statistically significant effect on these indices. This was partly due to large fluctuations in these parameters which occurred independent of the stimulus. Therefore it was concluded that these negative results were due to the intrinsic variability in these parameters and that an evaluation of cerebellar stimulation based on these indices was not adequate. Therefore, cross-correlation analysis was used to examine the effects of cerebellar stimulation on the excitability of neurons within the focus. This technique demonstrated that cerebellar stimulation modulated neuronal activity in the focus with 3 different profiles. These alterations in excitability were similar during the occurrence of either epileptic or non-epileptic activity in a single neuron. These results show that cerebellar stimulation can increase and decrease the excitability of neurons in an experimental seizure focus during both epileptic and non-epileptic activity.

A demonstration of the dentato-reticulospinal projection in the cat

Abstract Experiments were performed to anatomically and electrophysiologically demonstrate the existence of a dentato-reticulospinal pathway in the cat. Reticulospinal neurons projecting to the lumbar region of the spinal cord were shown to respond to stimulation in the dentate nucleus at latencies as short as 0.8 ms. The latency of these responses could be varied by changing either stimulus strength or stimulus frequency. Furthermore, intracellular recordings revealed that these responses were associated with a graded depolarization with latencies as short as 0.8 ms. Collision experiments confirmed that the responses recorded in reticular neurons following spinal cord stimulation were antidromically evoked and that the orthodromically evoked responses to dentate stimulation were conducted to the spinal cord. To ensure that the short latency responses evoked in these cells by dentate stimulation were not the result of activating a cerebellar projection to the brainstem through the inferior cerebellar peduncle, an experiment was performed demonstrating that these responses could be blocked by lesions of the brachium conjunctivum. In the anatomical experiments, small injections of horseradish peroxidase limited to the rostromedial region of the medullary reticular formation resulted in the retrograde labeling of neurons in the contralateral dentate nucleus. On the basis of these electrophysiological and neuroanatomical findings, it was concluded that a dentatoreticulospinal system is present in the cat. a system by which the dentate nucleus may affect neuronal integration occurring in the spinal cord.