The inhibitory 81yeine r~eptor (GlyR) i~ a liitand.gated chloride channel protein which dkpla),~ devdopmental heteroiLeneiiy in the mammalian central ncrvou~ ~y~tem. H©r~ wo descril~ 2 novel eDNA variants of the rat GlyR ~2 subunit and demonstrate that alternative ~pllcinll Ilenerate~ these 2 isoforms. The d¢dueed protein sequences (~2A and ~2B) exhibit 99~ identity wilh the previousl~¢ characterized human ~2 subunit. In site hy'bridizatt0n revealed expression of botll ",2A and crab raRNAs in the prenatal rat brain, suilgestinll that these variant protcin~l may have a role in synaptoilenesis. Heteroloilous expression in XenOl)US ooeytes showed that the more abtmdantll¢ ~xpre~d a2A subunit forms strychnlne..~asitiv~ ior ehannel~l which resemble human ~2 ~abunit GlyRs in their clectrophysiologieal properties.Glycine receptor; Alternative splicing; Receptor helcro~eneity: Brain development

The peripheral membrane protein gephyrin copurifies with the inhibitory glycine receptor of mammalian spinal cord. It binds with high affinity to polymerized tubulin and has been implicated in the anchoring of the glycine receptor to cytoskeletal elements. Recently, cDNA cloning has identified variants of the gephyrin mRNA, which originate from alternative splicing of four exonic regions (cassettes 1-4). In this study, the expression patterns of gephyrin splice variants were determined in the adult and developing rat brain by in situ hybridization with synthetic oligonucleotide probes. Gephyrin transcripts were detected throughout the brain and spinal cord, with mRNAs containing cassette 2 (C2 transcripts) being predominant in adult animals. C3 and C4 transcripts were seen in cerebellar granule cells and in the dentate gyrus, whereas a C1 probe did not produce detectable hybridization signals. During development, C2 and C3 mRNAs were found in most brain regions. Generally, the spatial and temporal distribution of gephyrin transcripts is similar to that of the glycine receptor beta subunit mRNA reported previously.

Synaptophysin and synaptoporin are two homologous integral membrane proteins of small synaptic vesicles. Here, the distribution of the corresponding transcripts in the CNS of the rat was investigated by in situ hybridization using sequence-specific oligonucleotide probes. Synaptophysin mRNA was abundantly distributed through all major brain regions, whereas synaptoporin transcripts displayed a more restricted localization in telencephalic structures. Resolution at the cellular level disclosed a differential labeling of distinct cell types in different areas, suggesting that synaptophysin and synaptoporin are expressed by specific subpopulations of central neurons. Consistent with this conclusion, relative synaptoporin mRNA contents were found to vary between different brain regions during postnatal development, whereas synaptophysin transcripts showed a more uniform increase during the same period.

During the past few decades, unexpected similarities have emerged between neurones and endocrine cells, especially in relation to secretion and secretory mechanisms. These two cell types are, in fact, recognized as having two parallel pathways of regulated secretion, the first sustained by synaptic-like vesicles (SLV), which predominate in most neurones where they are used for the release of classical, low-molecular weight neurotransmitters, and the second sustained by dense granules (DG) employed for the release of mixtures of compounds such as amines, proteins, peptides and nucleotides. The nature of the secretory products can also be identical in the two types of cell. For example, acetylcholine and GABA, considered until recently to be typical neurotransmitters, are also released by chromaffin and pancreatic â cells, respectively. The proteins of the chromogranin/secretogranin family, discovered in chromaffin and pituitary cells, are common to various types of neurone. Most importantly, the same integral membrane and soluble proteins known to govern the process of regulated exocytosis have been found to operate in both cell systems, including the SNAREs, the G proteins rab3A and B and the phosphoprotein rbSec1Ïmunc18 (S ollner et al. 1993;Jacobsson et al. 1994). Thus, in spite of their well-known structural and functional differences, the definition of 'neurosecretory' appears justified for both types of cell based on the common molecular properties of their secretory programme. In the present review, the ability of the cell to express this specific programme will be referred to as neurosecretion competence. Until recently, studies of neurosecretion competence were conducted primarily from the perspective of cellular differentiation. In various types of endocrine cells, the first traces of the specific hormone(s), accompanied by characteristic aspects of the phenotype, were observed to appear at distinct developmental stages and recognized to depend on the activity of multiple transcription factors expressed co-ordinately or in sequence during the course of differentiation (Groves et al. 1995;Anderson, 1997;Sosa-Pineda et al. 1997; St-Onge et al. 1997). However, whether the appearance of full neurosecretion competence depends exclusively on transcriptional events remains open to question. In fact (i) examples of divergence from the expected correlation between factor expression and phenotype acquisition have been reported (Schoenherr & Anderson, 1995;Scholl et al. 1996;Atouf et al. 1997), (ii) the

Upper-limb movement analysis is important to monitor objectively rehabilitation interventions, contributing to improving the overall treatments outcomes. Simple, fast, easy-to-use, and applicable methods are required to allow routinely functional evaluation of patients with different pathologies and clinical conditions. This paper describes the Reaching and Hand-to-Mouth Evaluation Method, a fast procedure to assess the upper-limb motor control and functional ability, providing a set of normative data from 42 healthy subjects of different ages, evaluated for both the dominant and the nondominant limb motor performance. Sixteen of them were reevaluated after two weeks to perform test-retest reliability analysis. Data were clustered into three subgroups of different ages to test the method sensitivity to motor control differences. Experimental data show notable test-retest reliability in all tasks. Data from older and younger subjects show significant differences in the measures related to the ability for coordination thus showing the high sensitivity of the method to motor control differences. The presented method, provided with control data from healthy subjects, appears to be a suitable and reliable tool for the upper-limb functional assessment in the clinical environment.

BackgroundA deep characterization of neurological patients is a crucial step for a detailed knowledge of the pathology and maximal exploitation and customization of the rehabilitation therapy. The muscle synergies analysis was designed to investigate how muscles coactivate and how their eliciting commands change in time during movement production. Few studies investigated the value of muscle synergies for the characterization of neurological patients before rehabilitation therapies. In this article, the synergy analysis was used to characterize a group of chronic poststroke hemiplegic patients.MethodsTwenty-two poststroke patients performed a session composed of a sequence of 3D reaching movements. They were assessed through an instrumental assessment, by recording kinematics and electromyography to extract muscle synergies and their activation commands. Patients’ motor synergies were grouped by the means of cluster analysis. Consistency and characterization of each cluster was assessed and clinically profiled by comparison with standard motor assessments.ResultsMotor synergies were successfully extracted on all 22 patients. Five basic clusters were identified as a trade-off between clustering precision and synthesis power, representing: healthy-like activations, two shoulder compensatory strategies, two elbow predominance patterns. Each cluster was provided with a deep characterization and correlation with clinical scales, range of motion, and smoothness.ConclusionThe clustering of muscle synergies enabled a pretherapy characterization of patients. Such technique may affect several aspects of the therapy: prediction of outcomes, evaluation of the treatments, customization of doses, and therapies.

The ankle represents a fairly complex bone structure, resulting in kinematics that hinders a flawless robot-assisted recovery of foot motility in impaired subjects. The paper proposes a novel device for ankle-foot neuro-rehabilitation based on a mechatronic redesign of the remarkable Agile Eye spherical robot on the basis of clinical requisites. The kinematic design allows the positioning of the ankle articular center close to the machine rotation center with valuable benefits in term of therapy functions. The prototype, named PKAnkle, Parallel Kinematic machine for Ankle rehabilitation, provides a 6-axes load cell for the measure of subject interaction forces/torques, and it integrates a commercial EMG-acquisition system. Robot control provides active and passive therapeutic exercises.

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