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Of all sensory cortical areas, barrel cortex is among the best understood in terms of circuitry, yet least understood in terms of sensory function. Because sensory cortical areas have stereotyped anatomies, understanding computations in one sensory area may inform us of computations being performed by other sensory areas or sensory microcircuits all over the brain. Functional studies of barrel cortex are therefore important for marrying our immense and increasing knowledge of the cortical circuitry with the computations being performed in a cortical microcircuit. This thesis is an investigation of barrel cortex function as it pertains to 1) site specific sensory evoked plasticity in cortical microcircuit and 2) sensory receptive fields of the different cortical lamina in S1. The brain's capacity to rewire is thought to diminish with age. It is widely believed that development stabilizes the synapses from thalamus to cortex and that adult experience alters only synaptic connections between cortical neurons. We combined whole-cell recording from individual thalamocortical neurons in adult rats with a newly developed automatic tracing technique to reconstruct individual axonal trees. Whisker trimming substantially reduced thalamocortical axon length in barrel cortex but not the density of TC synapses along a fiber. Thus, sensory experience alters the total number of TC synapses. After trimming, sensory stimulation evoked more tightly time-locked responses among thalamorecipient layer 4 cortical neurons. Axonal plasticity was topographically specific, with robust changes in L4 and modest changes in the septal and infragranular layers. These results indicate that plasticity is mediated by interactions with the local cortical subcircuit and may be suggestive of laminar specific roles in sensory learning/coding. Next we sought to examine spatiotemporal coding properties of neurons in the different layers of the cortical microcircuit in S1. We combined intracellular recording and a novel multi-directional multi-whisker stimulator system to estimate receptive fields by reverse correlation of stimuli to synaptic inputs. Spatiotemporal receptive fields were identified orders of magnitude faster than by conventional spike-based approaches, even for neurons with little or no spiking activity. Given a suitable stimulus representation, a simple linear model captured the stimulus-response relationship for all neurons with unprecedented accuracy. In contrast to conventional single-whisker stimuli, complex stimuli revealed dramatically sharpened receptive fields, largely due to the effects of adaptation. Surprisingly, this phenomenon allows the surround to facilitate rather than suppress responses to the principal whisker. Optimized stimuli enhanced firing in layers 4-6, but not 2/3, which remained sparsely active. Surround facilitation through adaptation may be required for discriminating complex shapes and textures during natural sensing.

Whether ongoing electroencephalogram (EEG) signal contributes to event related potential (ERP) generation is currently a matter of discussion for all sensory modalities. Resolving the controversy between additive and the oscillatory models has become crucial because evoked potentials are increasingly used in clinical practice as a physiological and neuropsychological index of brain areas or as a link with other functional approaches such as fMRI and the underlying network. The key issue is the search for a function underlying these mechanisms. Somatosensory evoked potentials are robust indicators of the afferent information at cortical level. In particular, the frontal N30 component of SEP can serve as a reliable physiological index of the dopaminergic motor pathway (Insola et al., 1999, Pierantozzi et al., 1999). Its properties in sensory-motor gating and cognitive processes make its fine analysis particularly interesting. The physiological interpretation and the origin of the frontal N30 are still debated (Allison et al., 1991, Cheron et al., 1994, Karnovsky et al., 1997, Balzamo et al., 2004, Barba et al., 2005). In this thesis we have investigated the mechanisms generating the N30 SEP component produced by electrical stimulation at median nerve at wrist, with reference to the current questioning of the additive and oscillatory models of the ERP (Sayers et al., 1974; Basar et al., 1980). We have applied analysis of the spectral content of neuronal oscillatory activity recorded in electroencephalographic (EEG) in order to study of dynamic brain processing underlying the N30 component. Concretely for studying whether the occurrence of the N30 related input induce amplitude modulation and/or reorganization of EEG rhythms we have analyzed separately power perturbation and phase synchrony of single EEG oscillations trials by means of event-related spectral perturbation (ERSP) and intertrial coherence (ITC) measurements. In addition, in order to model brain localizations of phase synchrony and power enhancement and to compare them to model localization of the N30 SEP we used swLORETA, a discrete method of source analysis. We have demonstrated that: (1) Ongoing EEG signals contribute to the generation of the N30 component (Cheron et al., 2007). (2) Dynamics of ongoing EEG signals underlie the specific behavior of the N30 during gating produced by movement execution (Cebolla et al., 2009). (3) Localization of brain sources generating the N30 SEP component overlaps those generating beta-gamma ongoing oscillations at the same short latency (Cebolla et al., 2010). Additionally the work developed during this thesis has served to develop a comprehensive, pragmatic paradigm to identify, evaluate and understand the somatosensory alterations in defined contexts, as illustrated by our recent work on perturbations and adaptations in astronauts over long term microgravity stay. We think that addressing this topic is essential in order to optimize and objectively evaluate adaptation to microgravity. We therefore proposed a detailed project to European Space Agency entitled “The frontal N30 somatosensory evoked potential for the study of sensory-motor and cognitive adaptations in weightlessness: NeuroSEP” (ILSRA 2009) in which we also proposed direct applications for quality of life aboard International Space Station, for the medical field and industry.

Thesis (Ph.D.). / Written for the Dept. of Neurology & Neurosurgery. Title from title page of PDF (viewed ). Errata sheets included. Includes bibliographical references.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.

No description available.

Three groups of rats were tested both before and after the bilateral ablation of the taste sensory cortex. The first group, exposed to quinine hydrochloride (QHCL) in a two-bottle preference situation, showed a large deficit postoperatively, but these were considerably reduced by the fourth postoperative week. A second group, tested for sodium chloride (NaCl) discrimination in a modified signal detection situation, also showed significant postoperative impairment. A third group, QHCL discrimination, was discarded for failure to learn the detection task. The results which were very unclear compared with NaCl discrimination and QHCL preference. It is concluded that preference tests are unsatisfactory measures of taste sensitivity unless the stimuli possess extreme aversive or preferred qualities. / Thesis / Master of Arts (MA)

Dravet syndrome (DS) is an infantile epileptic encephalopathy that is caused by loss-of-function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel, NaV1.1. Haploinsufficiency of NaV1.1 in DS patients leads to imbalanced excitability across brain circuits, resulting in a broad phenotypic profile including drug-resistant convulsive and non-convulsive (absence) seizures, cognitive impairment, ataxia, and sleep disruption. Dysfunction in the somatosensory corticothalamic (CT) circuit underlies several DS phenotypes including absence seizures and sleep disturbances. Yet, the precise mechanisms underlying somatosensory CT circuit dysfunction in DS remain unclear. Here, we sought to identify the cellular and synaptic mechanisms underlying somatosensory CT circuit dysfunction in a haploinsufficiency DS mouse model. This work reveals that NaV1.1 haploinsufficiency leads to cell-type-specific changes in the excitability of reticular thalamic (nRT), ventral posterolateral (VPL), and ventral posteromedial (VPM) neurons. Further, we identified alterations in both glutamatergic and GABAergic synaptic connectivity within the somatosensory CT circuit in DS mice. These findings introduce glutamatergic neuron dysfunction and synaptic alterations as novel disease mechanisms underlying thalamic circuit dysfunction in DS, providing new targets for therapeutic intervention. In addition, we reveal that VPL and VPM neurons exhibit distinct firing properties in a healthy CT circuit, suggesting they differentially contribute to circuit-wide function in health and dysfunction in disease. / Doctor of Philosophy / The brain is composed of biological circuits made up of excitatory and inhibitory neurons, which are connected through synapses. Proper balance between excitatory and inhibitory activity in these circuits is essential for maintaining healthy brain function. Dravet syndrome (DS) is an infantile-onset epilepsy caused by mutations in the SCN1A gene, which encodes the voltage-gated sodium channel, Nav1.1. Loss of this protein in the brain leads to an imbalance of excitation and inhibition across a variety of brain circuits, resulting in drug-resistant seizures and cognitive, motor, and learning deficits. Disrupted excitability in the somatosensory corticothalamic (CT) circuit specifically leads to non-convulsive seizures and sleep disruption in DS. However, the mechanisms underlying this circuit's dysfunction remain unclear. Revealing these mechanisms is critical for identifying therapeutic targets by which we can correct circuit function. In this work, we used a mouse model of DS to reveal changes in the excitability of three distinct cell populations of the somatosensory CT circuit. Importantly, changes were exhibited in both excitatory and inhibitory thalamic neuron populations. We further identified impairments in the synapses, both excitatory and inhibitory, connecting the somatosensory CT circuit. These cell-type-specific changes in excitability and synaptic connectivity provide novel targets for therapeutic intervention in DS.