Higher metal-ligand coordination in the catalytic site of cobalt-substituted Thermoanaerobacter brockii alcohol dehydrogenase lowers the barrier for enzyme catalysis.

Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) is a zinc-dependent NADP(+)/H-linked class enzyme that reversibly catalyzes the oxidation of secondary alcohols to their corresponding ketones. Cobalt substitution studies of other members of the alcohol dehydrogenase (ADH) family showed that the cobalt-containing ADHs have a similar active site structure but slightly decreased activity compared to wild-type zinc ADHs. In contrast, the cobalt-substituted TbADH (Co-TbADH) exhibits an increase in specific activity compared to the native enzyme [Bogin, O.

Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex.

A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical gamma-aminobutyric acid-ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles.

Information processing with frequency-dependent synaptic connections.

The efficacy of synaptic transmission between two neurons changes as a function of the history of previous activations of the synaptic connection. This history dependence can be characterized by examining the dependence of transmission on the frequency of stimulation. In this framework synaptic plasticity can also be examined in terms of changes in the frequency dependence of transmission and not merely in terms of synaptic strength which constitutes only a linear scaling mechanism.

Potential for multiple mechanisms, phenomena and algorithms for synaptic plasticity at single synapses.

Recent experimental evidence indicates that in the neocortex, the manner in which each synapse releases neurotransmitter in response to trains of presynaptic action potentials is potentially unique. These unique transmission characteristics arise because of a large heterogeneity in various synaptic properties that determine frequency dependence of transmission such as those governing the rates of synaptic depression and facilitation. A theoretical analysis was therefore undertaken to explore the phenomenologies of changes in the values of these synaptic parameters.

Differential signaling via the same axon of neocortical pyramidal neurons.

The nature of information stemming from a single neuron and conveyed simultaneously to several hundred target neurons is not known. Triple and quadruple neuron recordings revealed that each synaptic connection established by neocortical pyramidal neurons is potentially unique. Specifically, synaptic connections onto the same morphological class differed in the numbers and dendritic locations of synaptic contacts, their absolute synaptic strengths, as well as their rates of synaptic depression and recovery from depression.

Redistribution of synaptic efficacy between neocortical pyramidal neurons.

Experience-dependent potentiation and depression of synaptic strength has been proposed to subserve learning and memory by changing the gain of signals conveyed between neurons. Here we examine synaptic plasticity between individual neocortical layer-5 pyramidal neurons. We show that an increase in the synaptic response, induced by pairing action-potential activity in pre- and postsynaptic neurons, was only observed when synaptic input occurred at low frequencies.

The Drosophila Mutant tetanic Interacts with a Gene Complex Including the Structural Locus of K+ Channels and Shows Altered Dephosphorylation and Learning.

The tetanic (tta; X.-52.6) mutation has been isolated on the basis of its sensitivity to extradoses of the normal Shaker gene complex (ShC) where the K+ channel la is encoded.