Past events

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

Stimulus-specific adaptation is the decrease in the responses to a common stimulus that does not generalize, or generalize only partially, to other stimuli. Stimulus-specific adaptation in the auditory modality has been studied mostly with oddball sequences, which consist of a common and a rare stimuli. Recently, we started to use a number of other sound sequences in order to study the properties of adaptation in auditory cortex. I will show that (1) SSA is not only the result of the adaptation of the response to the common stimulus - in addition, the responses to the rare tones have a component due to the deviance of the rare tone relative to the regularity set by the common tone; (2) neuronal responses in auditory cortex of rats show sensitivity to finer types of statistical regularities; and (3) SSA can be evoked by other sounds as well, including sounds as similar to each other as two tokens of white noise. These results suggest the existence of a highly sensitive 'statistical machine' that analyzes and interprets the auditory scene.