Using retrograde transneuronal transfer of rabies virus in combination with a conventional tracer (cholera toxin B), we studied simultaneously direct (thalamocortical) and polysynaptic inputs to the ...ventral lateral intraparietal area (LIPv) and the medial intraparietal area (MIP) in nonhuman primates. We found that these areas receive major disynaptic inputs from specific portions of the cerebellar nuclei, the ventral dentate (D), and ventrolateral interpositus posterior (IP). Area LIPv receives inputs from oculomotor domains of the caudal D and IP. Area MIP is the target of projections from the ventral D (mainly middle third), and gaze- and arm-related domains of IP involved in reaching and arm/eye/head coordination. We also showed that cerebellar cortical “output channels” to MIP predominantly stem from posterior cerebellar areas (paramedian lobe/Crus II posterior, dorsal paraflocculus) that have the required connectivity for adaptive control of visual and proprioceptive guidance of reaching, arm/eye/head coordination, and prism adaptation. These findings provide important insight about the interplay between the posterior parietal cortex and the cerebellum regarding visuospatial adaptation mechanisms and visual and proprioceptive guidance of movement. They also have potential implications for clinical approaches to optic ataxia and neglect rehabilitation.
Neuronal activity encoding eye position and gaze signals participates in updating the spatial representations found in the posterior parietal cortex and is necessary for spatial accuracy in ...goal‐directed movements. Using retrograde transneuronal transfer of rabies virus in combination with a conventional tracer, we studied direct and polysynaptic inputs to the ventral lateral intraparietal area (LIPv) and medial intraparietal area (MIP) in non‐human primates, to identify possible sources of eye position and gaze signals. We found that these areas receive disynaptic inputs from the brainstem horizontal eye position integrator network (nucleus prepositus hypoglossi, PH) via the central lateral and ventral lateral thalamic nuclei. Our findings provide the first demonstration that inputs from the horizontal eye position integrator reach cortical areas. We found important topographical differences between PH populations targeting MIP and LIPv that likely reflect transmission of different types of eye movement signals. LIPv receives projections from the ipsilateral rostral PH, which may transmit ipsilateral eye position signals. In addition to inputs from the rostral PH, MIP receives strong projections from the contralateral caudal PH, which may contribute to both eye position and velocity signals. Unlike the horizontal integrator, we found that the vertical eye position integrator network, the interstitial nucleus of Cajal, does not project to these posterior parietal areas, in keeping with findings that the thalamic nuclei targeting LIPv and MIP receive almost exclusively horizontal oculomotor signals.
The posterior parietal cortex (PPC) integrates multisensory and motor‐related information for generating and updating body representations and movement plans. We used retrograde transneuronal ...transfer of rabies virus combined with a conventional tracer in macaque monkeys to identify direct and disynaptic pathways to the arm‐related rostral medial intraparietal area (MIP), the ventral lateral intraparietal area (LIPv), belonging to the parietal eye field, and the pursuit‐related lateral subdivision of the medial superior temporal area (MSTl). We found that these areas receive major disynaptic pathways via the thalamus from the nucleus of the optic tract (NOT) and the superior colliculus (SC), mainly ipsilaterally. NOT pathways, targeting MSTl most prominently, serve to process the sensory consequences of slow eye movements for which the NOT is the key sensorimotor interface. They potentially contribute to the directional asymmetry of the pursuit and optokinetic systems. MSTl and LIPv receive feedforward inputs from SC visual layers, which are potential correlates for fast detection of motion, perceptual saccadic suppression and visual spatial attention. MSTl is the target of efference copy pathways from saccade‐ and head‐related compartments of SC motor layers and head‐related reticulospinal neurons. They are potential sources of extraretinal signals related to eye and head movement in MSTl visual‐tracking neurons. LIPv and rostral MIP receive efference copy pathways from all SC motor layers, providing online estimates of eye, head and arm movements. Our findings have important implications for understanding the role of the PPC in representation updating, internal models for online movement guidance, eye‐hand coordination and optic ataxia.
With the use of rabies retrograde transneuronal tracing, we demonstrate in non‐human primates that cortical areas MSTl, LIPv and rostral MIP receive major ascending disynaptic pathways from the nucleus of the optic tract (NOT) and visual and motor layers of the superior colliculus (SC). Pathways from the NOT and SC visual layers serve to process the sensory consequences of slow eye movements for which the NOT is the key sensorimotor interface and are potential correlates for fast detection of motion, perceptual saccadic suppression and visual spatial attention. MSTl is the target of efference copy pathways from saccade‐ and head‐related compartments of SC upper motor layers, while LIPv and rostral MIP receive efference copy pathways from all SC motor layers and the underlying reticular formation, providing an online estimate of eye, head and arm movements.
The posterior parietal cortex (PPC) serves as an interface between sensory and motor cortices by integrating multisensory signals with motor‐related information. Sensorimotor transformation of ...somatosensory signals is crucial for the generation and updating of body representations and movement plans. Using retrograde transneuronal transfer of rabies virus in combination with a conventional tracer, we identified direct and polysynaptic somatosensory pathways to two posterior parietal areas, the ventral lateral intraparietal area (LIPv) and the rostral part of the medial intraparietal area (MIP) in macaque monkeys. In addition to direct projections from somatosensory areas 2v and 3a, respectively, we found that LIPv and MIP receive disynaptic inputs from the dorsal column nuclei as directly as these somatosensory areas, via a parallel channel. LIPv is the target of minor neck muscle‐related projections from the cuneate (Cu) and the external cuneate nuclei (ECu), and direct projections from area 2v, that likely carry kinesthetic/vestibular/optokinetic‐related signals. In contrast, MIP receives major arm and shoulder proprioceptive inputs disynaptically from the rostral Cu and ECu, and trisynaptically (via area 3a) from caudal portions of these nuclei. These findings have important implications for the understanding of the influence of proprioceptive information on movement control operations of the PPC and the formation of body representations. They also contribute to explain the specific deficits of proprioceptive guidance of movement associated to optic ataxia.
Purpose. Harmaline is one member of a class of tremorgenic harmala alkaloids that have been implicated in neuroprotective effects and neurodegenerative disorders. It has been reported to interact ...with several neurotransmitter receptors as well as ion exchangers and voltage-sensitive channels. One site of harmaline action in the brain is the inferior olive (IO). Either local or systemic harmaline injection has been reported to increase spiking rate and coherence in the inferior olive and this activation is thought to produce tremor and ataxia through inferior olivary neuron activation of target neurons in the cerebellum, but the cellular mechanism is not yet known. Methods. Here, we have performed whole cell voltage-clamp and current clamp recordings from olivary neurons in brain slices derived from newborn rats. Results. We found that both transient low-voltage activated (LVA) and sustained high voltage-activated (HVA) Ca2+ currents are significantly attenuated by 0.125 – 0.25 mM harmaline applied to the bath and that this attenuation is partially reversible. In current clamp recordings, spike-afterhyperpolarization complexes were evoked by brief positive current injections. Harmaline produced a small attenuation of spike amplitude, but large spike broadening associated with attenuation of the fast and medium afterhyperpolarization. Conclusion. Our data suggest that one mode of olivary neuron activation by harmaline involves attenuation of both HVA and LVA Ca2+ conductances and consequent attenuation of Ca2+-sensitive K+ conductances resulting in spike broadening and attenuation of the afterhyperpolarization. Both of HVA and LVA attenuation also suggests a role to regulate intracelluar Ca2+, thereby to protect neurons from apoptosis.
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Self‐motion detection requires the interaction of a number of sensory systems for correct perceptual interpretation of a given movement and an eventual motor response. Parietal cortical areas are ...thought to play an important role in this function, and we have thus studied the encoding of multimodal signals and their spatiotemporal interactions in the ventral intraparietal area of macaque monkeys. Thereby, we have identified for the first time the presence of vestibular sensory input to this area and described its interaction with somatosensory and visual signals, via extracellular single‐cell recordings in awake head‐fixed animals. Visual responses were driven by large field stimuli that simulated either backward or forward self‐motion (contraction or expansion stimuli, respectively), or movement in the frontoparallel plane (visual increments moving simultaneously in the same direction). While the dominant sensory modality in most neurons was visual, about one third of all recorded neurons responded to horizontal rotation. These vestibular responses were typically in phase with head velocity, but in some cases they could signal acceleration or even showed integration to position. The associated visual responses were always codirectional with the vestibular on‐direction, i.e. noncomplementary. Somatosensory responses were in register with the visual preferred direction, either in the same or in the opposite direction, thus signalling translation or rotation in the horizontal plane. These results, taken together with data on responses to optic flow stimuli obtained in a parallel study, strongly suggest an involvement of area VIP in the analysis and the encoding of self‐motion.
We recorded neuronal responses to optic flow stimuli in the ventral intraparietal area (VIP) of two awake macaque monkeys. According to previous studies on optic flow responses in monkey extrastriate ...cortex we used different stimulus classes: frontoparallel motion, radial stimuli (expansion and contraction) and rotational stimuli (clockwise and counter‐clockwise). Seventy‐five percent of the cells showed statistically significant responses to one or more of these optic flow stimuli. Shifting the location of the singularity of the optic flow stimuli within the visual field led to a response modulation in almost all cases. For the majority of neurons, this modulatory influence could be approximated in a statistically significant manner by a two‐dimensional linear regression. Gradient directions, derived from the regression parameters and indicating the direction of the steepest increase in the responses, were uniformly distributed. At the population level, an unbiased average response for the stimuli with different focus locations was observed. By applying a population code, termed ‘isofrequency encoding’, we demonstrate the capability of the recorded neuronal ensemble to retrieve the focus location from its population discharge. Responses to expansion and contraction stimuli cannot be predicted based on quantitative data on a neuron's frontoparallel preferred stimulus direction and the location and size of its receptive field. These results, taken together with data on polymodal motion responses in this area, suggest an involvement of area VIP in the analysis and the encoding of heading.
An important prerequisite for effective motor action is the discrimination between active and passive body movements. Passive
movements often require immediate reflexes, whereas active movements may ...demand suppression of the latter. The vestibular
system maintains correct body and head posture in space through reflexes. Since vestibular inputs have been reported to be
largely suppressed in the vestibular nuclei during active head movements, we investigated whether head movement-related signals
in the primate parietal cortex, a brain region involved in self-motion perception, could support both reflex functions and
self-movement behaviour. We employed a paradigm that made available direct comparison of neuronal discharge under active and
passive movement conditions. In this study, we demonstrate that a population of intraparietal (VIP (ventral) and MIP (medial))
cortex neurons change their preferred directions during horizontal head rotations depending on whether animals have performed
active movements, or if they were moved passively. In other neurons no such change occurred. A combination of these signals
would provide differential information about the active or passive nature of an ongoing movement. Moreover, some neurons'
responses clearly anticipated the upcoming active head movement, providing a possible basis for vestibular-related reflex
suppression. Intraparietal vestibular neurons thus distinguish between active and passive head movements, and their responses
differ substantially from those reported in brainstem vestibular neurons, regarding strength, timing, and direction selectivity.
We suggest that the contextual firing characteristics of these neurons have far-reaching implications for the suppression
of reflex movements during active movement, and for the representation of space during self-movement.
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