Past events

Patients with right hemisphere damage often exhibit a symptom complex where contra-lesional objects and events fail to induce an appropriate behavioral reaction. The most puzzling aspect of this syndrome - termed unilateral spatial neglect (USN) - is the failure of salient left-sided stimuli to attract attention and generate conscious perception. This phenomenon, which is often multi-modal, may happen in cases where the sensory pathways and the primary cortical areas are completely intact. Following a short description of the clinical manifestations, underlying anatomy and recovery patterns of USN, I will present data gathered in a series of studies done in our hospital, which aimed to clarify the nature of processing received by stimuli on the neglected side, and the effect of some theory-motivated manipulations aimed to ameliorate the impaired processing.

The neuronal alterations which occur in important neuron populations in young adult animals and changes in those processes which occur during aging and cause age-related learning deficits are beginning to be understood with cellular to systems level analyses. We have studied these processes with hippocampus-dependent trace eyeblink conditioning tasks. Calcium and calcium-activated potassium currents, that help control intrinsic neuronal excitability and are altered during learning and in aging, have been extensively studied. In vivo recording studies of CA1 hippocampal pyramidal neurons during and after associative eyeblink conditioning demonstrate functional alterations during learning and aging. We have examined mechanisms underlying these alterations in firing rate by examining CA1 neurons in brain slices. These current and voltage clamp studies of alterations in the calcium-activated potassium currents that increase neuronal excitability during associative learning in young animals and age-associated changes in these currents that occur in learning-impaired aging animals will be described. Behavioral pharmacological studies have demonstrated that age-associated behavioral changes can be reversed by compounds targeting neuronal excitability. Intracellular signaling pathways and alterations in calcium currents that may lead to these changes in intrinsic excitability during learning are being explored.

Pyramidal neurons in supragranular layers II and III of rodent sensory cortices are a main target of ascending sensory information conveyed by columnar projections of layer IV as well as contextual information from neighboring columns or higher cortical areas. However, layer II is not separable from layer III on cytoarchitectonic grounds. We therefore investigated to which extent pyramidal neurons in the supragranular layers differ in their input-output connectivity. We obtained detailed spatial maps of layer-specific intracortical functional input connectivity for electrophysiologically and morphologically identified supragranular pyramidal neurons by combining local photolysis of caged glutamate with whole-cell patch-clamp recordings using biocytin-containing pipettes in rat barrel cortex in vitro. The main source of excitatory inputs onto all supragranular pyramidal cells was layer IV of the same column. This translaminar excitatory source was even more prominent than local and transcolumnar excitatory inputs from within the supragranular layers, both in density and strength. Additionally, many pyramidal neurons received a prominent excitatory layer Va input, often originating from beyond the “home” column. Among those pyramidal neurons we detected a significantly higher fraction of cells located in a putative layer II than in TZ or putative layer III. Our results indicate a strong but differential information transmission from layer IV as well as layer Va, both important cortical entry points for parallel streams of sensory information, toward the supragranular layers. Within supragranular layers, information processing in pyramidal neurons can be "fine tuned" through local and transcolumnar excitatory networks. Finally this integrated information is forwarded with a prominent transcolumnar component by putative layer II pyramidal cells but with an intracolumnar preponderance, including significant layer IV-backprojections, by putative layer III pyramidal neurons