Objective detection of microtremors in netrin-G2 knockout mice.

BACKGROUND: Essential tremor is the most prevalent movement disorder and is thought to be caused by abnormalities in the cerebellar system; however, its underlying neural mechanism is poorly understood. In this study, we found that mice lacking netrin-G2, a cell adhesion molecule which is expressed in neural circuits related to the cerebellar system, exhibited a microtremor resembling an essential tremor. However, it was difficult to quantify microtremors in netrin-G2 KO mice. NEW METHOD: We developed a new tremor detector which can quantify the intensity and frequency of a tremor. RESULTS: Using this system, we were able to characterize both the microtremors in netrin-G2 KO mice and low-dose harmaline-induced tremors which, to date, had been difficult to detect. Alcohol and anti-tremor drugs, which are effective in decreasing the symptoms of essential tremor in patients, were examined in netrin-G2 KO mice. We found that some drugs lowered the tremor frequency, but had little effect on tremor intensity. Forced swim as a stress stimulus in netrin-G2 KO mice dramatically enhanced tremor symptoms. COMPARISON WITH EXISTING METHODS: The detection performance even for tremors induced by low-dose harmaline was similar to that in previous studies or more sensitive than the others. CONCLUSIONS: Microtremors in netrin-G2 KO mice are reliably and quantitatively detected by our new tremor detection system. We found different effects of medicines and factors between human essential tremors and microtremors in netrin-G2 KO mice, suggesting that the causations, mechanisms, and symptoms of tremors vary and are heterogeneous, and the objective analyses are required.

The claustrum coordinates cortical slow-wave activity.

During sleep and awake rest, the neocortex generates large-scale slow-wave (SW) activity. Here, we report that the claustrum coordinates neocortical SW generation. We established a transgenic mouse line that enabled the genetic interrogation of a subpopulation of claustral glutamatergic neurons. These neurons received inputs from and sent outputs to widespread neocortical areas. The claustral neuronal firings mostly correlated with cortical SW activity. In vitro optogenetic stimulation of the claustrum induced excitatory postsynaptic responses in most neocortical neurons, but elicited action potentials primarily in inhibitory interneurons. In vivo optogenetic stimulation induced a synchronized down-state featuring prolonged silencing of neural activity in all layers of many cortical areas, followed by a down-to-up state transition. In contrast, genetic ablation of claustral neurons attenuated SW activity in the frontal cortex. These results demonstrate a crucial role of claustral neurons in synchronizing inhibitory interneurons across wide cortical areas for the spatiotemporal coordination of SW activity.

Anisotropy in the representation of direction preferences in cat area 18.

Higher visual cortical areas are involved in the perception of complex stimuli, such as the optic flow created by self-motion. On the other hand, area 18 is thought to extract primitive visual features, feeding higher cortical areas for further processing. In this study, we applied optical imaging of intrinsic signals in the central, lower visual field of cat area 18, and reconstructed direction preference and direction selectivity maps in each hemisphere. We observed a significant overrepresentation of downward and temporal directions, in accordance with previous electrophysiological results. Cardinal orientations were not overrepresented, however. Downward directions were overrepresented at the highest direction selectivity domains. Temporal direction representation, on the other hand, decreased with direction selectivity. Our findings therefore suggest the existence of a neural substrate for the processing of optic flow in cat area 18.

Online analysis method for intrinsic signal optical imaging.

The intrinsic optical imaging technique has been widely applied for the visualization of functional maps in the sensory cortices of mammals. Many current studies refer this mapping in order to focus thereafter on particular features, at some particular locations: a fast and accurate mapping is therefore required. However, even during a successful experiment, the recorded raw data are usually contaminated by some kinds of noise that cannot necessarily be averaged out over the trials. An adequate image data analysis method has to be applied to extract signals closely related neural activities in response to presented stimuli. Thus far two different analysis methods could be adopted: the band-pass filtering and the GIF method [Yokoo T, Knight BW, Sirovich L. An optimization approach to signal extraction from noisy multivariate data. NeuroImage 2001:14;1309-26]. While the latter one is very efficient but requires the whole data in order to maximize the signal to noise ratio, the simple band-pass filtering technically reaches its limits very quickly. Here we propose another filtering method based on the polynomial subtraction of spatially smoothly modulated components. This simple method can visualize well-organized iso-orientation domains of the cat visual cortex with reliability similar to more sophisticated ones while allowing an online visualization of the clean data.

Spatial patterns of excitation and inhibition evoked by lateral connectivity in layer 2/3 of rat barrel cortex.

In the rat barrel cortex, neurons in layer 4 are topographically arranged in a precise columnar structure, and the excitatory feed-forward input from layer 4 to layer 2/3 projects almost exclusively within the home barrel column. Here we analyzed the lateral connectivity that links neighboring columns in layer 2/3, which is necessary for integrating information across whiskers. We examined the spatial distributions of three different functional types of lateral connections in layer 2/3 of the rat barrel cortex: glutamate receptor-mediated excitatory connections, GABA(A) receptor-mediated inhibitory connections and GABA(B) receptor-mediated inhibitory connections. Synaptic potentials of pyramidal neurons, which are measures of the strength of connections, were evoked by a horizontal array of stimulation electrodes. The synaptic potentials and their decrease with distance from the stimulation site were measured in two types of slices whose planes were parallel to or orthogonal to barrel rows. Excitatory and GABA(B) receptor-mediated inhibitory connections were stronger along barrel rows than across them, whereas GABA(A) receptor-mediated inhibitory connections did not show such a tendency. These results indicate that lateral connectivity in layer 2/3 varies on the basis of not only excitatory polarity but also receptor subtypes.