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Objective: to investigate the prevalence and risk factors of diabetes to dementia and its subtypes such as Alzheimer disease (AD) and vascular dementia (VD) among the Chinese elderly population., Methods: among 8,213 Chinese people aged 65 years and older, 1,109 subjects with type 2 diabetes millitus (T2DM) were ascertained by interview and direct glucose testing. All diabetic subjects were initially screened with the "DSM-IV criteria" for dementia and its subtypes. We compared the prevalence of dementia in diabetic patients with that in ordinary subjects, and analyzed the association of the status of diabetes with dementia including AD and VD. Logistic regression was used to assess OR of dementia and its subtypes with T2DM., Results: after a comprehensive geriatric and cognitive assessment, 132 diabetic subjects were diagnosed with all-cause dementia. The prevalence rate for dementia with T2DM was 1.61%. Of demented subjects, 37 subjects had AD, 30 subjects had VD. The prevalence rates for AD with T2DM and VD with T2DM were 4.51% and 3.65%, respectively. In the univariate analyses, among all diabetic subjects, compared with cognitive intactly subjects, the demented subjects, including AD and VD subjects, were older, more female had higher percentage of current smoking, had a greater duration of diabetes, took more frequent use of diabetes medications, and stronger effect of APOE ε4 status. In multivariate logistic regression analyses, variables including age, APOE ε4 allele, duration from onset of diabetes, using oral hypoglycemic agents, HMG-CoA reductase (statins) were significantly associated with increased risk for dementia with T2DM (all P < 0.05)., Conclusions: the present study shows that T2DM is associated with dementia and its subtypes amongst elderly people in the Chinese population.

Dopamine (DA) is an important modulator of synaptic transmission and plasticity that is causally involved in fundamental brain functions and dysfunctions. We examined the dopaminergic modulation of synaptic transmission and sensory responses in telencephalic area Dp of zebrafish, the homolog of olfactory cortex. By combining anatomical tracing and immunohistochemistry, we detected no DA neurons in Dp itself but long-range dopaminergic input from multiple other brain areas. Whole-cell recordings revealed no obvious effects of DA on membrane potential or input resistance in the majority of Dp neurons. Electrical stimulation of the olfactory tracts produced a complex sequence of synaptic currents in Dp neurons. DA selectively decreased inhibitory currents with little or no effect on excitatory components. Multiphoton calcium imaging showed that population responses of Dp neurons to olfactory tract stimulation or odor application were enhanced by DA, consistent with its effect on inhibitory synaptic transmission. These effects of DA were blocked by an antagonist of D2-like receptors. DA therefore disinhibits and reorganizes sensory responses in Dp. This modulation may affect sensory perception and could be involved in the experience-dependent modification of odor representations.

In the olfactory bulb, the modulatory neurotransmitter dopamine (DA) is coexpressed with GABA by local interneurons, but its role in odor processing remains obscure. We examined functions of DA mediated by D₂-like receptors in the olfactory bulb of adult zebrafish by pharmacology, whole-cell recordings, calcium imaging, and optogenetics. Bath application of DA had no detectable effect on odorant-evoked sensory input. DA directly hyperpolarized mitral cells (MCs) via D₂-like receptors and slightly increased their response gain. Consistent with this effect on input-output functions of MCs, small odorant responses were suppressed, whereas strong responses were enhanced in the presence of DA. These effects increased the root-mean-square contrast of population activity patterns but did not reduce their correlations. Optical stimulation of interneurons expressing channelrhodopsin-2 evoked fast GABAergic inhibitory currents in mitral cells but failed to activate D₂ receptor-mediated currents when stimuli were short. Prolonged stimulus trains, however, activated a slow hyperpolarizing current that was blocked by an antagonist of D₂-like receptors. GABA and DA are therefore both released from interneurons by electrical activity and hyperpolarize MCs, but D₂-dependent dopaminergic effects occur on slower timescales. Additional effects of DA may be mediated by D₁-like receptors. These results indicate that DA acts on D₂-like receptors via asynchronous release and/or volume transmission and implicate DA in the slow adaptation of circuit function. The shift of the membrane potential away from spike threshold could adapt mitral cells to background input without compromising their sensitivity.

Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons (mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes., (©2011 Macmillan Publishers Limited. All rights reserved)

The light-gated cation channel channelrhodopsin-2 (ChR2) has been used in a variety of model systems to investigate the function of complex neuronal networks by stimulation of genetically targeted neurons. In slice physiology, ChR2 opens the door to novel types of experiments and greatly extends the technical possibilities offered by traditional electrophysiology. In this short review, we first consider several technical aspects concerning the use of ChR2 in slice physiology, providing examples from our own work. More specifically, we discuss differences between light-evoked action potentials and spontaneous or electrically induced action potentials. Our work implies that light-evoked action potentials are associated with increased calcium influx and a very high probability of neurotransmitter release. Furthermore, we point out the factors limiting the spatial resolution of ChR2 activation. Secondly, we discuss how synaptic transmission and plasticity can be studied using ChR2. Postsynaptic depolarization induced by ChR2 can be combined with two-photon glutamate uncaging to potentiate visually identified dendritic spines. ChR2-mediated stimulation of presynaptic axons induces neurotransmitter release and reliably activates postsynaptic spines. In conclusion, ChR2 is a powerful tool to investigate activity-dependent changes in structure and function of synapses.

The conditional expression of transgenes at high levels in sparse and specific populations of neurons is important for high-resolution optogenetic analyses of neuronal circuits. We explored two complementary methods, viral gene delivery and the iTet-Off system, to express transgenes in the brain of zebrafish. High-level gene expression in neurons was achieved by Sindbis and Rabies viruses. The Tet system produced strong and specific gene expression that could be modulated conveniently by doxycycline. Moreover, transgenic lines showed expression in distinct, sparse and stable populations of neurons that appeared to be subsets of the neurons targeted by the promoter driving the Tet-activator. The Tet system therefore provides the opportunity to generate libraries of diverse expression patterns similar to gene trap approaches or the thy-1 promoter in mice, but with the additional possibility to pre-select cell types of interest. In transgenic lines expressing channelrhodopsin-2, action potential firing could be precisely controlled by two-photon stimulation at low laser power, presumably because the expression levels of the Tet-controlled genes were high even in adults. In channelrhodopsin-2-expressing larvae, optical stimulation with a single blue LED evoked distinct swimming behaviors including backward swimming. These approaches provide new opportunities for the optogenetic dissection of neuronal circuit structure and function.