Cerebellar afferents from neurons in the extraocular motor nuclei: a fluorescent retrograde double-labeling study in the sheep. (1/323)

The fluorescent retrograde double labeling technique has been used to identify within the extraocular motor nuclei of the sheep the neurons projecting to the cerebellum and to provide evidence whether they are motor neurons sending collaterals to the cerebellum or a separate population of neurons. The study was performed on eight sheep. The fluorescent tracers used were Fast Blue and the diamidino yellow dihydrochloride. In one and the same animal a fluorescent tracer was injected into the extraocular muscles (EOMs) and the other into bilateral points of the vermal folia II-V and paramedian lobule, or into the vermal folia VI, VIIA and VIIB, or into the underlying fastigial nuclei. Within the oculomotor, trochlear, and abducens nuclei, almost all of the motor neurons were labeled by the tracer injected into the EOMs and only a few cells were fluorescent for the tracer infiltrated into the cerebellum. These latter labelings were present bilaterally, and their number and distribution did not show apparent differences after injecting the paramedian lobule and the vermal folia or the fastigial nucleus. Along the rostrocaudal extent of the oculomotor and trochlear nuclei, the neurons projecting to the cerebellum were intermingled with the motor neurons located in the nuclear area facing the medial longitudinal fasciculus. In the abducens nucleus they were restricted to the caudal pole of the nucleus, which is located ventrolaterally to the genu of the facial nerve. Double-labeled neurons were never found. The absence of double-labeled cells, in spite of the efficiency of the tracer infiltration into the EOMs and into the cerebellum, demonstrates that the cerebellar projections from the extraocular motor nuclei are not collaterals of the motor neurons, but axons of a separate population of neurons.  (+info)

Role of the Botzinger complex in fastigial nucleus-mediated respiratory responses. (2/323)

We have reported that the phrenic neurogram (PN) is modulated by stimulation of the fastigial nucleus (FN) of the cerebellum. The present study was undertaken to search for brainstem site(s) involved in the FN efferent pathway to modulate phrenic nerve activities. Experiments were performed on 35 anesthetized, paralyzed, and ventilated cats, using the PN as the index of the respiratory motor output. Results showed that bilateral electrolytic lesions of the red nucleus (RN), the paramedian reticular nucleus (PRN), or the pontine respiratory group (PRG) had little effect on the ability of FN stimulation to modulate the respiratory output. However, the modulation was abolished by bilateral electrolytic lesions of the Botzinger complex (BotC). Further studies showed that bilateral chemical inactivation of BotC neurons produced by topical microinjection of kainic acid or cobalt chloride failed to abolish the modulation. We concluded that fibers of passage, not synapses or cell bodies in the BotC, were involved in the modulatory effect of FN stimulation on the PN. The RN, PRN, and PRG appear not to be important in the neural circuitry responsible for the FN modulation of the phrenic activity.  (+info)

Perineuronal nets of proteoglycans in the adult mouse brain, with special reference to their reactions to Gomori's ammoniacal silver and Ehrlich's methylene blue. (3/323)

As our previous studies have indicated, many subsets of neurons in the vertebrate brain possess a sulfated proteoglycan surface coat which reacts to cationic iron colloid and aldehyde fuchsin. The present study demonstrated that this surface coat is supravitally stained with Ehrlich's methylene blue, and doubly with this blue and aldehyde fuchsin, a finding suggesting its being identical to Cajal's superficial reticulum (red superficial) and to Golgi's reticular coating (revetement reticulare). The perineuronal surface coat was further stained with Gomori's ammoniacal silver, and doubly with this silver and cationic iron colloid. These neurons with such a proteoglycan surface coat usually expressed cell surface glycoproteins which were labeled with lectin Wisteria floribunda agglutinin. Hyaluronidase digestion did not interfere with this lectin labeling of the glycoproteins, methylene blue and Gomori's ammoniacal silver staining of the surface coat, while it erased the cationic iron colloid and aldehyde fuchsin staining of the surface coat. These findings suggest that the perineuronal proteoglycan surface coat is associated with some additional molecules which are resistant to hyaluronidase digestion and stainable with methylene blue and Gomori's ammoniacal silver. The possibility is suggested that these molecules might represent "ligand proteoglycans" connecting the perineuronal proteoglycans and cell surface glycoproteins.  (+info)

Intrinsic neurons of fastigial nucleus mediate neurogenic neuroprotection against excitotoxic and ischemic neuronal injury in rat. (4/323)

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) and arterial pressure (AP) and provides long-lasting protection against focal and global ischemic infarctions. We investigated which neuronal element in FN, perikarya or axons, mediates this central neurogenic neuroprotection and whether it also protects against excitotoxicity. In anesthetized rats, the FN was stimulated for 1 hr, and ibotenic acid (IBO) was microinjected unilaterally into the striatum. In unstimulated controls, the excitotoxic lesions averaged approximately 40 mm3. Stimulation of FN, but not dentate nucleus (DN), significantly reduced lesion volumes up to 80% when IBO was injected 15 min, 72 hr, or 10 d, but not 30 d, thereafter. In other rats, intrinsic neurons of FN or DN were destroyed by pretreatment with IBO. Five days later, the FN was stimulated, and 72 hr later, IBO was microinjected into the striatum. Lesions of FN, but not DN, abolished neuroprotection but not the elevations of rCBF and AP elicited from FN stimulation. Excitotoxic lesions of FN, but not DN, also abolished the 37% reduction in focal ischemic infarctions produced by middle cerebral artery occlusion. Excitation of intrinsic FN neurons provides long-lasting, substantial, and reversible protection of central neurons from excitotoxicity, as well as focal ischemia, whereas axons in the nucleus, probably collaterals of ramified brainstem neurons, mediate the elevations in rCBF, which do not contribute to neuroprotection. Long-lived protection against a range of injuries is an unrecognized function of FN neurons transmitted over pathways distinct from those regulating rCBF.  (+info)

Fastigial nucleus activity during different frequencies and orientations of vertical vestibular stimulation in the monkey. (5/323)

Neurons in the rostral part of the fastigial nucleus (FN) respond to vestibular stimulation but are not related to eye movements. To understand the precise role of these vestibular-only neurons in the central processing of vestibular signals, unit activity in the FN of alert monkeys (Macaca mulatta) was recorded. To induce vestibular stimulation, the monkey was rotated sinusoidally around an earth-fixed horizontal axis at stimulus frequencies between 0.06 (+/-15 degrees) and 1.4 Hz (+/-7.5 degrees). During stimulation head orientation was changed continuously, allowing for roll, pitch, and intermediate planes of orientation. At a frequency of 0.6 Hz, 59% of the neurons had an optimal response orientation (ORO) and a null response (i.e., no modulation) 90 degrees apart. The phase of neuronal response was constant except for a steep shift of 180 degrees around the null response. This group I response is compatible with a semicircular canal input, canal convergence, or a single otolith input. Several other features indicated more complex responses, including spatiotemporal convergence (STC). 1) For 35% of the responses at 0.6 Hz, phase changes were gradual with different orientations. Fifteen percent of these had a null response (group II), and 20% showed only a minimal response but no null response (group III). The remaining responses (6%), classified as group IV, were characterized by a constant sensitivity at different orientations in most instances. 2) For the vast majority of neurons, the stimulus frequency determined the response group, i.e., an individual neuron could show a group I response at one frequency and a group II (III or IV) response at another frequency. 3) ORO changed with frequency by >45 degrees for 44% of the neurons. 4) Although phase changes at different frequencies were close to head velocity (+/-45 degrees ) or head position (+/-45 degrees ) for most neurons, they exceeded 90 degrees for 29% of the neurons between 0.1 and 1.0 Hz. In most cases, this was a phase advance. The change in sensitivity with change in frequency showed a similar pattern for all neurons; the average sensitivity increased from 1.24 imp. s-1. deg-1 at 0.1 Hz to 2.97 imp. s-1. deg-1 at 1.0 Hz. These data demonstrate that only an analysis based on measurements at different frequencies and orientations reveals a number of complex features. They moreover suggest that for the vast majority of neurons several sources of canal and otolith information interact at this central stage of vestibular information processing.  (+info)

Simulations of cerebellar motor learning: computational analysis of plasticity at the mossy fiber to deep nucleus synapse. (6/323)

We question the widely accepted assumption that a molecular mechanism for long-term expression of synaptic plasticity is sufficient to explain the persistence of memories. Instead, we show that learning and memory require that these cellular mechanisms be correctly integrated within the architecture of the neural circuit. To illustrate this general conclusion, our studies are based on the well characterized synaptic organization of the cerebellum and its relationship to a simple form of motor learning. Using computer simulations of cerebellar-mediated eyelid conditioning, we examine the ability of three forms of plasticity at mossy fiber synapses in the cerebellar nucleus to contribute to learning and memory storage. Results suggest that when the simulation is exposed to reasonable patterns of "background" cerebellar activity, only one of these three rules allows for the retention of memories. When plasticity at the mossy fiber synapse is controlled by nucleus or climbing fiber activity, the circuit is unable to retain memories because of interactions within the network that produce spontaneous drift of synaptic strength. In contrast, a plasticity rule controlled by the activity of the Purkinje cell allows for a memory trace that is resistant to ongoing activity in the circuit. These results suggest specific constraints for theories of cerebellar motor learning and have general implications regarding the mechanisms that may contribute to the persistence of memories.  (+info)

Lateral cerebellar hemispheres actively support sensory acquisition and discrimination rather than motor control. (7/323)

This study examined a new hypothesis proposing that the lateral cerebellum is not activated by motor control per se, as widely assumed, but is engaged during the acquisition and discrimination of tactile sensory information. This proposal derives from neurobiological studies of these regions of the rat cerebellum. Magnetic resonance imaging of the lateral cerebellar output nucleus (dentate) of humans during passive and active sensory tasks confirmed four a priori implications of this hypothesis. Dentate nuclei responded to cutaneous stimuli, even when there were no accompanying overt finger movements. Finger movements not associated with tactile sensory discrimination produced no dentate activation. Sensory discrimination with the fingers induced an increase in dentate activation, with or without finger movements. Finally, dentate activity was greatest when there was the most opportunity to modulate the acquisition of the sensory tactile data: when the discrimination involved the active repositioning of tactile sensory surface of the fingers. Furthermore, activity in cerebellar cortex was strongly correlated with observed dentate activity. This distinct four-way pattern of effects strongly challenges other cerebellar theories. However, contrary to appearances, neither our hypothesis nor findings conflict with behavioral effects of cerebellar damage, neurophysiological data on animals performing motor tasks, or cerebellar contribution to nonmotor, perceptual, and cognitive tasks.  (+info)

Single-unit evidence for eye-blink conditioning in cerebellar cortex is altered, but not eliminated, by interpositus nucleus lesions. (8/323)

Many theories of motor learning explain learning-related changes in motor behavior in terms of plasticity in the cerebellar cortex. Empirical evidence, however, does not always appear to be consistent with such formulations. It is the anterior cerebellar interpositus nucleus (aINP) that seems to be essential for acquisition and retention of conditioned eye-blink responses under most circumstances and it has been therefore suggested that the aINP is the critical site of learning-related plasticity during eye-blink conditioning. Supporting this conclusion are studies demonstrating that multiple-unit conditioning-related neural activity patterns observed in many brain regions disappear after aINP lesion. The possibility that the cerebellar cortex may be involved in forming these patterns has not been assessed adequately, however. In the current study, trained rabbits received kainic acid lesions of the INP. After recovery, the animals underwent additional sessions of conditioning during which single-unit activity was recorded from the cerebellar cortex. Our results suggest that the aINP is not the sole site of plasticity during eye-blink conditioning, as a subset of the neurons recorded from lesioned animals demonstrated conditioning-related firing patterns. The lesions did change the character of these firing patterns from those observed in saline controls, however, in ways that can be generally described as a loss of organization. The normal tendency for the population of cortical cells to change firing rate together, for instance, was significantly less noticeable in lesioned animals. These results suggest that the aINP may be involved in the production of important features of conditioned responding, such as system timing function, therefore suggesting the need for more models that incorporate aINP and brain stem feedback as integral to the production of organized neural and behavioral responses.  (+info)