Effects of Nucleus Prepositus Hypoglossi Lesions on Visual Climbing Fiber Activity in the Rabbit Flocculus

2000 ◽  
Vol 84 (5) ◽  
pp. 2552-2563 ◽  
Author(s):  
M. P. Arts ◽  
C. I. De Zeeuw ◽  
J. Lips ◽  
E. Rosbak ◽  
J. I. Simpson

The caudal dorsal cap (dc) of the inferior olive is involved in the control of horizontal compensatory eye movements. It provides those climbing fibers to the vestibulocerebellum that modulate optimally to optokinetic stimulation about the vertical axis. This modulation is mediated at least in part via an excitatory input to the caudal dc from the pretectal nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system. In addition, the caudal dc receives a substantial GABAergic input from the nucleus prepositus hypoglossi (NPH). To investigate the possible contribution of this bilateral inhibitory projection to the visual responsiveness of caudal dc neurons, we recorded the climbing fiber activity (i.e., complex spikes) of vertical axis Purkinje cells in the flocculus of anesthetized rabbits before and after ablative lesions of the NPH. When the NPH ipsilateral to the recorded flocculus was lesioned, the spontaneous complex spike firing frequency did not change significantly; but when both NPHs were lesioned, the spontaneous complex spike firing frequency increased significantly. When only the contralateral NPH was lesioned, the spontaneous complex spike firing frequency decreased significantly. Neither unilateral nor bilateral lesions had a significant influence on the depth of complex spike modulation during constant velocity optokinetic stimulation or on the transient continuation of complex spike modulation that occurred when the constant velocity optokinetic stimulation stopped. The effects of the lesions on the spontaneous complex spike firing frequency could not be explained when only the projections from the NPH to the inferior olive were considered. Therefore we investigated at the electron microscopic level the nature of the commissural connection between the two NPHs. The terminals of this projection were found to be predominantly GABAergic and to terminate in part on GABAergic neurons. When this inhibitory commissural connection is taken into consideration, then the effects of NPH lesions on the spontaneous firing frequency of floccular complex spikes are qualitatively explicable in terms of relative weighting of the commissural and caudal dc projections of the NPH. In summary, we conclude that in the anesthetized rabbit the inhibitory projection of the NPH to the caudal dc influences the spontaneous firing frequency of floccular complex spikes but not their modulation by optokinetic stimulation.

2018 ◽  
Author(s):  
Chiheng Ju ◽  
Laurens W.J. Bosman ◽  
Tycho M. Hoogland ◽  
Arthiha Velauthapillai ◽  
Pavithra Murugesan ◽  
...  

AbstractCerebellar Purkinje cells integrate sensory information with motor efference copies to adapt movements to behavioural and environmental requirements. They produce complex spikes that are triggered by the activity of climbing fibres originating in neurons of the inferior olive. These complex spikes can shape the onset, amplitude and direction of movements as well as the adaptation of such movements to sensory feedback. Clusters of nearby inferior olive neurons project to parasagittally aligned stripes of Purkinje cells, referred to as “microzones”. It is currently unclear to what extent individual Purkinje cells within a single microzone integrate climbing fibre inputs from multiple sources of different sensory origins, and to what extent sensory-evoked climbing fibre responses depend on the strength and recent history of activation. Here we imaged complex spike responses in cerebellar lobule crus 1 to various types of sensory stimulation in awake mice. We find that different sensory modalities and receptive fields have a mild, but consistent, tendency to converge on individual Purkinje cells. Purkinje cells encoding the same stimulus show increased events with coherent complex spike firing and tend to lie close together. Moreover, whereas complex spike firing is only mildly affected by variations in stimulus strength, it strongly depends on the recent history of climbing fibre activity. Our data point towards a mechanism in the olivo-cerebellar system that regulates complex spike firing during mono- or multisensory stimulation around a relatively low set-point, highlighting an integrative coding scheme of complex spike firing under homeostatic control.


2000 ◽  
Vol 84 (6) ◽  
pp. 2945-2960 ◽  
Author(s):  
Maninder Kahlon ◽  
Stephen G. Lisberger

We followed simple- and complex-spike firing of Purkinje cells (PCs) in the floccular complex of the cerebellum through learned modifications of the pursuit eye movements of two monkeys. Learning was induced by double steps of target speed in which initially stationary targets move at a “learning” speed for 100 ms and then change to either a higher or lower speed in the same direction. In randomly interleaved control trials, targets moved at the learning speed in the opposite direction. When the learning direction was theon direction for simple-spike responses, learning was associated with statistically significant changes in simple-spike firing for 10 of 32 PCs. Of the 10 PCs that showed significant expressions of learning, 8 showed changes in simple-spike output in the expected direction: increased or decreased firing when eye acceleration increased or decreased through learning. There were no statistically significant changes in simple-spike responses or eye acceleration during pursuit in the control direction. When the learning direction was in the off direction for simple-spike responses, none of 15 PCs showed significant correlates of learning. Although changes in simple-spike firing were recorded in only a subset of PCs, analysis of the population response showed that the same relationship between population firing and eye acceleration obtained before and after learning. Thus learning is associated with changes that render the modified population response appropriate to drive the changed behavior. To analyze complex-spike firing during learning we correlated complex-spike firing in the second, third, and fourth 100 ms after the onset of target motion with the retinal image motion in the previous 100 ms. Data were largely consistent with previous evidence that image motion drives complex spikes with a direction selectivity opposite that for simple spikes. Comparison of complex-spike responses at different times after the onset of control and learning target motions in the learning direction implied that complex spikes could guide learning during decreases but not increases in eye acceleration. Learning caused increases or decreases in the sensitivity of complex spikes to image motion in parallel with changes in eye acceleration. Complex-spike responses were similar in all PCs, including many in which learning did not modify simple-spike responses. Our data do not disprove current theories of cerebellar learning but suggest that these theories would have to be modified to account for simple- and complex-spike firing of floccular Purkinje cells reported here.


2003 ◽  
Vol 90 (4) ◽  
pp. 2349-2357 ◽  
Author(s):  
Daniel A. Nicholson ◽  
John H. Freeman

The development of synaptic interconnections between the cerebellum and inferior olive, the sole source of climbing fibers, could contribute to the ontogeny of certain forms of motor learning (e.g., eyeblink conditioning). Purkinje cell complex spikes are produced exclusively by climbing fibers and exhibit short- and long-latency activity in response to somatosensory stimulation. Previous studies have demonstrated that evoked short- and long-latency complex spikes generally occur on separate trials and that this response segregation is regulated by inhibitory feedback to the inferior olive. The present experiment tested the hypothesis that complex spikes evoked by periorbital stimulation are regulated by inhibitory feedback from the cerebellum and that this feedback develops between postnatal days (PND) 17 and 24. Recordings from individual Purkinje cell complex spikes in urethan-anesthetized rats indicated that the segregation of short- and long-latency evoked complex spike activity emerges between PND17 and PND24. In addition, infusion of picrotoxin, a GABAA-receptor antagonist, into the inferior olive abolished the response pattern segregation in PND24 rats, producing evoked complex spike response patterns similar to those characteristic of younger rats. These data support the view that cerebellar feedback to the inferior olive, which is exclusively inhibitory, undergoes substantial changes in the same developmental time window in which certain forms of motor learning emerge.


2010 ◽  
Vol 68 ◽  
pp. e435 ◽  
Author(s):  
Miho Onizuka ◽  
Nicolas Schweighofer ◽  
Yuichi Katori ◽  
Kazuyuki Aihara ◽  
Keisuke Toyama ◽  
...  

1990 ◽  
Vol 63 (5) ◽  
pp. 1262-1275 ◽  
Author(s):  
L. S. Stone ◽  
S. G. Lisberger

1. We report the complex-spike responses of two groups of Purkinje cells (P-cells). The cell were classified according to their simple-spike firing during smooth eye movements evoked by visual and vestibular stimuli with the use of established criteria (Lisberger and Fuchs 1978; Stone and Lisberger 1990). During pursuit with the head fixed, ipsi gaze-velocity P-cells (GVP-cells) showed increased simple-spike firing when gaze moved toward the side of the recording, whereas down GVP-cells showed increased simple-spike firing when gaze moved downward. 2. During pursuit of sinusoidal target motion, the complex-spike firing rate was modulated out-of-phase with the simple-spike firing rate. Ipsi GVP-cells showed increased complex-spike firing during pursuit away from the side of the recording, and down GVP-cells showed increased complex-spike firing during upward pursuit. The strength of the complex-spike response increased as a function of the frequency of sinusoidal target motion. 3. GVP-cells showed directionally selective complex-spike responses during the initiation of pursuit to ramp target motion. Ipsi GVP-cells had increased complex-spike firing 100 ms after the onset of contralaterally directed target motion and decreased complex-spike activity after the onset of ipsilaterally directed target motion. Down GVP-cells had increased complex-spike firing 100 ms after the onset of upward target motion and decreased firing after the onset of downward target motion. As during sinusoidal target motion, each cell's simple- and complex-spike responses had the opposite directional preferences. 4. When the monkeys fixated a stationary target during a transient vestibular stimulus, the retinal slip caused by the 14-ms latency of the vestibuloocular reflex (VOR) affected the complex-spike firing rate. For ipsi GVP-cells, ipsilateral head motion caused transient contralateral image motion and an increase in complex-spike firing. The same vestibular stimulus in darkness caused an almost identical eye movement but had no effect on complex-spike firing. We conclude that complex spikes in ipsi GVP-cells are driven by contralaterally directed image motion. 5. To determine the events surrounding complex-spike firing during pursuit, we triggered averages of eye and target velocity on the occurrence of complex spikes during pursuit of sine-wave target motion. The averages revealed a transient pulse of retinal image motion that peaked approximately 100 ms before the complex spike. We conclude that complex spikes during steady-state pursuit are driven by the retinal slip associated with imperfect pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)


2013 ◽  
Vol 109 (2) ◽  
pp. 389-404 ◽  
Author(s):  
Yasuhiko Saito ◽  
Yuchio Yanagawa

Spontaneous miniature outward currents (SMOCs) are known to exist in smooth muscles and peripheral neurons, and evidence for the presence of SMOCs in central neurons has been accumulating. SMOCs in central neurons are induced through Ca2+-activated K+(KCa) channels, which are activated through Ca2+-induced Ca2+release from the endoplasmic reticulum via ryanodine receptors (RyRs). Previously, we found that some neurons in the prepositus hypoglossi nucleus (PHN) showed spontaneous outward currents (SOCs). In the present study, we used whole cell recordings in slice preparations of the rat brain stem to investigate the following: 1) the ionic mechanisms of SOCs, 2) the types of neurons exhibiting frequent SOCs, and 3) the effect of Ca2+-activated conductance on neuronal firing. Pharmacological analyses revealed that SOCs were induced via the activation of small-conductance-type KCa(SK) channels and RyRs, indicating that SOCs correspond to SMOCs. An analysis of the voltage responses to current pulses of the fluorescence-expressing inhibitory neurons of transgenic rats revealed that inhibitory neurons frequently exhibited SOCs. Abolition of SOCs via blockade of SK channels enhanced the frequency of spontaneous firing of inhibitory PHN neurons. However, abolition of SOCs via blockade of RyRs reduced the firing frequency and hyperpolarized the membrane potential. Similar reductions in firing frequency and hyperpolarization were also observed when Ca2+-activated nonselective cation (CAN) channels were blocked. These results suggest that, in inhibitory neurons in the PHN, Ca2+release via RyRs activates SK and CAN channels, and these channels regulate spontaneous firing in a complementary manner.


1983 ◽  
Vol 50 (5) ◽  
pp. 1197-1219 ◽  
Author(s):  
T. W. Berger ◽  
P. C. Rinaldi ◽  
D. J. Weisz ◽  
R. F. Thompson

Extracellular single-unit recordings from neurons in the CA1 and CA3 regions of the dorsal hippocampus were monitored during classical conditioning of the rabbit nictitating membrane response. Neurons were classified as different cell types using response to fornix stimulation (i.e., antidromic or orthodromic activation) and spontaneous firing characteristics as criteria. Results showed that hippocampal pyramidal neurons exhibit learning-related neural plasticity that develops gradually over the course of classical conditioning. The learning-dependent pyramidal cell response is characterized by an increase in frequency of firing within conditioning trials and a within-trial pattern of discharge that correlates strongly with amplitude-time course of the behavioral response. In contrast, pyramidal cell activity recorded from control animals given unpaired presentations of the conditioned and unconditioned stimulus (CS and UCS) does not show enhanced discharge rates with repeated stimulation. Previous studies of hippocampal cellular electrophysiology have described what has been termed a theta-cell (19-21, 45), the activity of which correlates with slow-wave theta rhythm generated in the hippocampus. Neurons classified as theta-cells in the present study exhibit responses during conditioning that are distinctly different than pyramidal cells. theta-Cells respond during paired conditioning trials with a rhythmic bursting; the between-burst interval occurs at or near 8 Hz. In addition, two different types of theta-cells were distinguishable. One type of theta-cell increases firing frequency above pretrial levels while displaying the theta bursting pattern. The other type decreases firing frequency below pretrial rates while showing a theta-locked discharge. In addition to pyramidal and theta-neurons, several other cell types recorded in or near the pyramidal cell layer could be distinguished. One cell type was distinctive in that it could be activated with a short, invariant latency following fornix stimulation, but spontaneous action potentials of such neurons could not be collided with fornix shock-induced action potentials. These neurons exhibit a different profile of spontaneous firing characteristics than those of antidromically identified pyramidal cells. Nevertheless, neurons in this noncollidable category display the same learning-dependent response as pyramidal cells. It is suggested that the noncollidable neurons represent a subpopulation of pyramidal cells that do not project an axon via the fornix but project, instead, to other limbic cortical regions.(ABSTRACT TRUNCATED AT 400 WORDS)


2018 ◽  
Vol 120 (4) ◽  
pp. 1525-1533
Author(s):  
Yue Zhang ◽  
Yuchio Yanagawa ◽  
Yasuhiko Saito

We previously reported that cholinergic current responses mediated via nicotinic acetylcholine (ACh) receptors (nAChRs) in the prepositus hypoglossi nucleus (PHN), which participates in gaze control, can be classified into distinct types based on different kinetics and are mainly composed of α7- and/or non-α7-subtypes: fast (F)-, slow (S)-, and fast and slow (FS)-type currents. In this study, to clarify how each current type is related to neuronal activities, we investigated the relationship between the current types and the membrane properties and the firing responses that were induced by each current type. The proportion of the current types differed in neurons that exhibited different afterhyperpolarization (AHP) profiles and firing patterns, suggesting that PHN neurons show a preference for specific current types dependent on the membrane properties. In response to ACh, F-type neurons showed either one action potential (AP) or multiple APs with a short firing duration, and S-type neurons showed multiple APs with a long firing duration. The firing frequency of F-type neurons was significantly higher than that of S-type and FS-type neurons. An α7-subtype-specific antagonist abolished the firing responses of F-type neurons and reduced the responses of FS-type neurons but had little effect on the responses of S-type neurons, which were reduced by a non-α7-subtype-specific antagonist. These results suggest that the different properties of the current types and the distinct expression of the nAChR subtypes in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs. NEW & NOTEWORTHY Prepositus hypoglossi nucleus (PHN) neurons show distinct nicotinic acetylcholine receptor (nAChR)-mediated current responses. The proportion of the current types differed in the neurons that exhibited different afterhyperpolarization profiles and firing patterns. The nAChR-mediated currents with different kinetics induced firing responses of the neurons that were distinct in the firing frequency and duration. These results suggest that the different properties of the current types in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs.


2007 ◽  
Vol 16 (4-5) ◽  
pp. 209-215
Author(s):  
Joseph M. Furman ◽  
Mark S. Redfern ◽  
Rolf G. Jacob

Previous studies of vestibulo-ocular function in patients with anxiety disorders have suggested a higher prevalence of peripheral vestibular dysfunction compared to control populations, especially in panic disorder with agoraphobia. Also, our recent companion studies have indicated abnormalities in postural control in patients with anxiety disorders who report a high degree of space and motion discomfort. The aim of the present study was to assess the VOR, including the semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular canal-otolith interaction, in a well-defined group of patients with anxiety disorders. The study included 72 patients with anxiety disorders (age 30.6 +/− 10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus; 11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic anxiety. Patients were further categorized based on the presence (45 of 72) or absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of 72) of excessive space and motion discomfort (SMD). Sinusoidal and constant velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used to assess both the otolith-ocular reflex and static semicircular canal-otolith interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal-otolith interaction. The eye movement response to rotation was measured using bitemporal electro-oculography. Results showed a significantly higher VOR gain and a significantly shorter VOR time constant in anxiety patients. The effect of anxiety on VOR gain was significantly greater in patients without SMD as compared to those with SMD. Anxiety patients without height phobia had a larger OVAR modulation. We postulate that in patients with anxiety, there is increased vestibular sensitivity and impaired velocity storage. Excessive SMD and height phobia seem to have a mitigating effect on abnormal vestibular sensitivity, possibly via a down-weighting of central vestibular pathways.


2006 ◽  
Vol 95 (4) ◽  
pp. 2342-2351 ◽  
Author(s):  
Beerend Winkelman ◽  
Maarten Frens

The climbing fibers (CFs) that project from the dorsal cap of the inferior olive (IO) to the flocculus of the cerebellar cortex have been reported to be purely sensory, encoding “retinal slip.” However, a clear oculomotor projection from the nucleus prepositus hypoglossi (NPH) to the IO has been shown. We therefore studied the sensorimotor information that is present in the CF signal. We presented rabbits with visual motion noise stimuli to break up the tight relation between instantaneous retinal slip and eye movement. Strikingly, the information about the motor behavior in the CF signal more than doubled that of the sensory component and was time-locked more tightly. The contribution of oculomotor signals was independently confirmed by analysis of spontaneous eye movements in the absence of visual input. The motor component of the CF code is essential to distinguish unexpected slip from self-generated slip, which is a prerequisite for proper oculomotor learning.


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