long-term-sensory-conflict-in-freely-behaving-mice

Long-term Sensory Conflict in Freely Behaving Mice

Long-term sensory conflict protocols are a valuable means of studying motor learning. The presented protocol produces a persistent sensory conflict for ...

in-vivo-intracerebral-stereotaxic-injections-for-optogenetic

In Vivo Intracerebral Stereotaxic Injections for Optogenetic Stimulation of Long-Range Inputs in Mouse Brain Slices

Knowledge of cell-type specific synaptic connectivity is a crucial prerequisite for understanding brain-wide neuronal circuits. The functional ...

CNRS

Université Paris Descartes

CNRS (Integrative Neuroscience and Cognition Center, UMR 8002)

Université Paris Descartes, Sorbonne Paris Cité

Vestibular compensation following unilateral labyrinthectomy is associated with modifications of the membrane and firing properties of central vestibular neurons. To determine whether gap junctions could be involved in this process, immunofluorescent detection of neuronal connexin 36 and astrocytic connexin 43 was performed in the medial vestibular nucleus (MVN) of rats. In non-lesioned animals, strong staining was observed with anti-connexin 43 antibodies, while moderate staining was obtained with the anti-connexin 36 antibody. However, the expression of either type of connexin was not modified following unilateral labyrinthectomy. These morphological observations were complemented by pharmacological tests performed during extracellular recordings of MVN neurons in guinea pig brainstem slices. In non-lesioned animals, the gap junction blocker carbenoxolone reversibly decreased or suppressed the spontaneous discharge of about 60% of MVN neurons. This reduction was often associated with a long-duration disruption of the regularity of spike discharge. Both effects were mimicked by several other gap junction blockers, but not by glycyrrhizic acid, an analog of carbenoxolone that does not block gap junctions but reproduces its non-specific effects, nor by the selective inhibitor of astrocytic connexin-based networks endothelin-1. Similar effects of carbenoxolone were obtained on the spontaneous activity of ipsilesional MVN neurons recorded in brainstem slices taken from labyrinthectomized animals. Altogether, these results suggest that neuronal gap junctions are involved in shaping the spontaneous activity of MVN neurons. However, unilateral labyrinthectomy does not affect the expression of gap junctions in vestibular nuclei nor their implication in the regulation of neuronal activity.

Evidence against a role of gap junctions in vestibular compensation.

Many mutant mouse strains display pathological behaviors, such as head tilts, head bobbing, or circling and waltzing, strongly suggesting that their vestibular system is impaired. Recently, Yoder and Taube studied head direction signals in tilted mutant mice, which have an impaired gravitation sensitivity in the vestibular periphery. Here we summarize their findings and discuss a caveat related to the general use of mutant mouse strains in systems physiology.

Impaired perception of gravity leads to altered head direction signals: what can we learn from vestibular-deficient mice?

The vestibular organs consist of complementary sensors: the semicircular canals detect rotations while the otoliths detect linear accelerations, including the constant pull of gravity. Several fundamental questions remain on how the vestibular system would develop and/or adapt to prolonged changes in gravity such as during long-term space journey. How do vestibular reflexes develop if the appropriate assembly of otoliths and semi-circular canals is perturbed? The aim of present work was to evaluate the role of gravity sensing during ontogeny of the vestibular system. In otoconia-deficient mice (ied), gravity cannot be sensed and therefore maculo-ocular reflexes (MOR) were absent. While canals-related reflexes were present, the ied deficit also led to the abnormal spatial tuning of the horizontal angular canal-related VOR. To identify putative otolith-related critical periods, normal C57Bl/6J mice were subjected to 2G hypergravity by chronic centrifugation during different periods of development or adulthood (Adult-HG) and compared to non-centrifuged (control) C57Bl/6J mice. Mice exposed to hypergravity during development had completely normal vestibulo-ocular reflexes 6 months after end of centrifugation. Adult-HG mice all displayed major abnormalities in maculo-ocular reflexe one month after return to normal gravity. During the next 5 months, adaptation to normal gravity occurred in half of the individuals. In summary, genetic suppression of gravity sensing indicated that otolith-related signals might be necessary to ensure proper functioning of canal-related vestibular reflexes. On the other hand, exposure to hypergravity during development was not sufficient to modify durably motor behaviour. Hence, 2G centrifugation during development revealed no otolith-specific critical period.

Mathieu Beraneck

Integrative Neuroscience and Cognition Center,
UMR8002,
Integrative Neuroscience and Cognition Center, UMR8002

CNRS

Long-term Sensory Conflict in Freely Behaving Mice

In Vivo Intracerebral Stereotaxic Injections for Optogenetic Stimulation of Long-Range Inputs in Mouse Brain Slices

Mathieu Beraneck

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CNRS

Long-term Sensory Conflict in Freely Behaving Mice

In Vivo Intracerebral Stereotaxic Injections for Optogenetic Stimulation of Long-Range Inputs in Mouse Brain Slices

Integrative Neuroscience and Cognition Center,
UMR8002,
Integrative Neuroscience and Cognition Center, UMR8002