A spinal organ of proprioception for integrated motor action feedback

Proprioception is essential for behavior and provides a sense of our body movements in physical space. Proprioceptor organs are thought to be only in the periphery. Whether the central nervous system can intrinsically sense its own movement remains unclear. Here we identify a segmental organ of proprioception in the adult zebrafish spinal cord, which is embedded by intraspinal mechanosensory neurons expressing Piezo2 channels. These cells are late-born, inhibitory, commissural neurons with unique molecular and physiological profiles reflecting a dual sensory and motor function. The central proprioceptive organ locally detects lateral body movements during locomotion and provides direct inhibitory feedback onto rhythm-generating interneurons responsible for the central motor program. This dynamically aligns central pattern generation with movement outcome for efficient locomotion. Our results demonstrate that a central proprioceptive organ monitors self-movement using hybrid neurons that merge sensory and motor entities into a unified network

A Novel Neural Substrate for the Transformation of Olfactory Inputs into Motor Output

Anatomical and physiological experiments in the lamprey reveal the neural circuit involved in transforming olfactory inputs into motor outputs, which was previously unknown in a vertebrate

Reversible Disruption of Pre-Pulse Inhibition in Hypomorphic-Inducible and Reversible CB1-/- Mice

Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes). Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout (-/-) mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1-/-) only in absence of doxycycline (Dox). In such mice, under Dox+ or vehicle, as well as in wild-type (WT) and CB1-/-, two endophenotypes motor activity (increased in animal models of schizophrenia) and pre-pulse inhibition (PPI) of startle reflex (disrupted in schizophrenia) were analyzed. Both CB1-/- and IRh-CB1-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1-/- animals, was on the contrary highly and significantly disrupted only in Dox+ IRh-CB1-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in schizophrenia and in other psychiatric disorders

Chloride conductance produces both presynaptic inhibition and antidromic spikes in primary afferents.

International audiencePrimary afferents from a crayfish leg proprioceptor display both primary afferent depolarizations (PADs) and antidromic spikes. PADs are generated by activation of GABA receptors and produce presynaptic inhibition, while the antidromic spikes do not elicit any synaptic effect in the postsynaptic neurons. The aim of the present study was to investigate the ionic mechanisms that allow PADs to produce antidromic spikes and to test whether GABA can produce similar effects. Intracellular recordings from the sensory axon terminals within the ganglion where PAD are produced were performed. Lowering the extracellular chloride concentration resulted in an increase in PAD amplitude, which was then capable of producing antidromic spikes. Local application of GABA close to the axon terminal also resulted in production of antidromic spikes. We conclude that antidromic spikes may result from the activation of a GABA-mediated increase in chloride conductance that also produces PADs. Therefore PADs and antidromic spikes may represent two aspects of the same GABAergic inhibitory mechanism that gate sensory transmission

Direct evidence for presynaptic inhibitory mechanisms in crayfish sensory afferents.

International audience1. The central control of sensory inputs from a proprioceptor [chordotonal organ (CO)] in the second joint [coxo-basipodite (CB)] of the fifth leg was studied in crayfish in vitro preparations (Fig. 1A). Simultaneous intracellular recordings from CBCO terminals (CBT) and postsynaptic motoneurons (MNs) were performed along with micropipette pressure ejection or bath application of gamma-aminobutyric acid (GABA), to study the presynaptic mechanisms at work in the CBT (Fig. 1B). 2. Two intracellular recordings were used to show that the spikes never overshoot, and that the more central the recording site within the neuropile, the smaller the spikes (Fig. 2). Only electrotonic conduction occurs, therefore, in the sensory afferents within the ganglion. 3. Pressure ejection of GABA close to the recording site of CBTs in the ganglion (Fig. 3A) gave rise to a membrane depolarization, the reversal potential of which was about -25 mV (Fig. 7), as well as to an increase in the membrane conductance (Fig. 3C) and a decrease in the orthodromic spike amplitude; moreover, it did not elicit either hyperpolarization, or any change in the membrane conductance of the postsynaptic MN (Fig. 3B), which indicates that pressure ejection of GABA affected only a restricted area around the CBT and not the postsynaptic MNs. 4. In CBT, spontaneous primary afferent depolarizations (PADs) occurred irregularly when the activity of the preparation was not rhythmic (Fig. 4A), and in bursts when the preparation displayed fictive locomotion (Fig. 4B). In the latter case, antidromic spikes were sometimes superimposed on PADs (Fig. 4D). The amplitude of the PADs was reduced when picrotoxin (PTX), a GABA antagonist, was applied (Fig. 5), which suggests that GABA may be involved in spontaneous PADs. The reversal potential of PADs was about -25 mV (Figs. 6 and 7). 5. During simultaneous recordings from a CBT and a monosynaptically related MN, GABA applied by pressure ejection close to the CBT (Fig. 8A) completely suppressed the excitatory postsynaptic potentials (EPSPs) elicited by CBT spikes in the MN (Fig. 8, B and D). This was due to a presynaptic mechanism because no change in the membrane potential or membrane conductance was observed in the MN (Fig. 8C) and most of the CBTs associated with a given MN were affected (Fig. 9). 6. Simultaneously recording from a CBT and a monosynaptically related MN demonstrated that, during bouts of PADs, the spike amplitude decreased in proportion to the PAD amplitude (Fig. 10A).(ABSTRACT TRUNCATED AT 400 WORDS

Monosynaptic connections mediate resistance reflex in crayfish (Procambarus clarkii) walking legs

International audienc

Presynaptic inhibition and antidromic discharges in crayfish primary afferents.

The mechanisms of presynaptic inhibition have been studied in sensory afferents of a stretch receptor in an in vitro preparation of the crayfish. Axon terminals of these sensory afferents display primary afferent depolarisations (PADs) mediated by the activation of GABA receptors that open chloride channels. Intracellular labeling of sensory axons by Lucifer yellow combined with GABA immunohistochemistry revealed the presence of close appositions between GABA-immunoreactive boutons and sensory axons close to their first branching point within the ganglion. Electrophysiological studies showed that GABA inputs mediating PADs appear to occur around the first axonal branching point, which corresponds to the area of transition between active and passive propagation of spikes. Moreover, this study demonstrated that whilst shunting appeared to be the sole mechanism involved during small amplitude PADs, sodium channel inactivation occurred with larger amplitude PADs. However, when the largest PADs (>25 mV) are produced, the threshold for spike generation is reached and antidromic action potentials are elicited. The mechanisms involved in the initiation of antidromic discharges were analyzed by combining electrophysiological and simulation studies. Three mechanisms act together to ensure that PAD-mediated spikes are not conveyed distally: 1) the lack of active propagation in distal regions of the sensory axons; 2) the inactivation of the sodium channels around the site where PADs are produced; and 3) a massive shunting through the opening of chloride channels associated with the activation of GABA receptors. The centrally generated spikes are, however, conveyed antidromically in the sensory nerve up to the proprioceptive organ, where they inhibit the activity of the sensory neurons for several hundreds of milliseconds