The role of glyclinergic interneurons in the dorsal column nuclei

[Abstract] The aim of this paper is to provide new insights about the circuitry and the role of the dorsal column nuclei (DCN) in processing somatosensory information. The presence of glycinergic cells, a second type of DCN interneurons in addition to well-known GABAergic interneurons, opens the door to more complex interactions between cuneate cells as well as to a new hypothesis about the computational implications of such interactions. The research posed here fits in a broader context in the field of the sensory systems and deals with the general issue on the role of subcortical structures (i.e the thalamus) in processing sensory information

cuneate spiking neural network learning to classify naturalistic texture stimuli under varying sensing conditions

Abstract We implemented a functional neuronal network that was able to learn and discriminate haptic features from biomimetic tactile sensor inputs using a two-layer spiking neuron model and homeostatic synaptic learning mechanism. The first order neuron model was used to emulate biological tactile afferents and the second order neuron model was used to emulate biological cuneate neurons. We have evaluated 10 naturalistic textures using a passive touch protocol, under varying sensing conditions. Tactile sensor data acquired with five textures under five sensing conditions were used for a synaptic learning process, to tune the synaptic weights between tactile afferents and cuneate neurons. Using post-learning synaptic weights, we evaluated the individual and population cuneate neuron responses by decoding across 10 stimuli, under varying sensing conditions. This resulted in a high decoding performance. We further validated the decoding performance across stimuli, irrespective of sensing velocities using a set of 25 cuneate neuron responses. This resulted in a median decoding performance of 96% across the set of cuneate neurons. Being able to learn and perform generalized discrimination across tactile stimuli, makes this functional spiking tactile system effective and suitable for further robotic applications

Cortical modulation of dorsal column nuclei: a computational study

[Abstract] We present a computational study aimed at exploring the sensorimotor cortex modulation of the behaviour of dorsal column nuclei, specifically the impact of synaptic parameters, during both sleep and waking conditions. On the basis of the circuit proposed by Canedo et al. (2000), we have developed realistic computational models that have been tested with simultaneous electrocorticographic as well as intracellular cuneate recordings performed in anaesthetized cats. The results show that, (1) under sleep conditions, the model can block the transmission of afferent sensory information and, (2) operations expected during wakefulness, such as filtering and facilitation, can be performed if synaptic parameters are appropriately tuned.Argentina. Consejo Interinstitucional de Ciencia y Tecnología; PB01-121212Xunta de Galicia; XU02–211

Modelo dinámico de la circuitería push-pull del dLGN

El núcleo geniculado lateral dorsal (dNGL) es la entrada principal de la información visual a la corteza visual primaria (V1). La función que siempre se le ha atribuido, es la de una mera estación de relevo, es decir, que no realiza ningún tipo de procesamiento relevante de la información que procede de las células ganglionares. El complejo esquema de la circuitería existente entre las células de relevo y ganglionares nos hace dudar de tal afirmación. En la presente tesis planteamos como el dNGL podría estar transformando el mensaje que la retina envía a V1. Para ello hemos creado modelos computacionales basados en evidencias experimentales, que nos permiten analizar el tipo de codificación espacio-temporal que se están llevando a cabo sobre los estímulos visuales

DNaseI Hypersensitivity and Ultraconservation Reveal Novel, Interdependent Long-Range Enhancers at the Complex Pax6 Cis-Regulatory Region

The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6(Sey/Sey) mice

Analysis of HOXA5 expression and function in development of the central nervous system

The Hox genes encode transcription factors that are indispensable for proper spatio-temporal patterning of the vertebrate body axes. In mouse, Hoxa5 transcripts are differentially expressed in specific mesoderm-derived structures and in the most anterior domain of expression in the central nervous system (CNS). However, the functional significance of any pattern of protein-coding RNAs must be verified by correlating the presence of the protein(s) and RNAs. Here we describe the dynamic pattern of HOXA5 protein during mouse embryogenesis. The HOXA5 protein is detected as early as embryonic day (E) 9.0, and is found, as development proceeds, in several mesoderm-derived structures. In addition, the protein shows a strikingly restricted and dynamic expression pattern in the developing CNS, and is detected in both motor neurons and interneurons between E10.5-E13.5. In many mesoderm-derived tissues affected by the Hoxa5 mutation, the expression pattern of HOXA5 protein corresponds to that of the putative functional Hoxa5 transcript. However, in the CNS, this correlation is exclusively demonstrated in the most anterior domain of expression. We next focused on a complex HOXA5 expression pattern in the caudal hindbrain. In this structure, we show that HOXA5 expression is confined to the caudal region of the developing inferior olivary nucleus (ION) and dorsal lamella of the dorsal accessory olive (DAO) subnucleus. Furthermore, the ION can be transiently defined by a combinatorial expression of BRN3A and LIM1/2 transcription factors that may belong to a new dorsal neuron cell type in the caudal hindbrain defined in this study. Although HOXA5 is dispensable for the transcriptional code of ION up to embryonic day (E) 16.5, the protein expression is crucial to preserve BRN3A expression in the dorsal lamella of DAO at E18.5. To date, this is the first report for expression of any Hox5 paralog in ION. Our results suggest that HOXA5 plays a strong role in maintaining the normal transcriptional code for ION, which may affect establishment of connectivity, maturation, and synaptic stabilization of climbing fibers developed postnatally. Overall, the HOXA5 protein pattern is consistent with its proposed role in positional specification in mesodermal structures, as well as in the embryonic neuraxis

Editorial: The olivo-cerebellar system

Investigation on the olivo-cerebellum system has attained a high level of sophistication leading to define several structural and functional properties of neurons, synapses, connections and circuits. Research has expanded and deepened in so many directions, and so many theories and models have been proposed, that an ensemble review of the matter is now neede

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems