Hidekazu Kaneko

Induction of stable long‐term depression in vivo in the hippocampal–prefrontal cortex pathway

We studied excitatory field potentials in the medial prefrontal cortex (mPFC, prelimbic area) to electrostimulation of the ventral hippocampus (CA1/subicular region) in the anaesthetized rat. Nine hundred stimulus trains (5 pulses at 250 Hz) applied at 1 Hz to the ventral hippocampus significantly and persistently depressed the amplitude and maximal slope (∼ 55% for each index) of the prelimbic field potentials, but did not change the latency of the maximal slope or peak negativity. Twelve stimulus trains (50 pulses at 250 Hz) applied subsequently at 0.1 Hz restored the depression back to control level, and this reversible depression was maintained for at least 13 h. Cumulative depressive effects on the prelimbic field potential amplitude and maximal slope were observed upon addition of stimulus trains in the hippocampus. An important implication of the results is that the direct pathway from the hippocampus to the mPFC in the rat retains long‐term depression (LTD) as a neuroplastic form in vivo. This form could cooperate with long‐term potentiation (LTP) and such a bi‐directional synaptic plasticity in the prefrontal cortex contributes to how cortical neural networks store information.

Preparatory inhibition of cortico-spinal excitability: a transcranial magnetic stimulation study in man

In order to investigate the preparatory modulations of cortico-spinal excitability, reaction time (RT) methods were combined with transcranial magnetic stimulation (TMS) of the motor cortex. We analyzed the variations in the amplitude of motor potentials evoked in a prime mover (flexor digitorum sublimis) by TMS delivered during the foreperiod of a visual choice RT task. In experiment 1 (n = 10), the TMS was delivered either simultaneously with the warning signal or simultaneously with the response signal in two conditions of foreperiod duration: short (500 ms) and long (2500 ms). The peak amplitude of the motor evoked potentials diminished during the short foreperiod but not during the long foreperiod. Since RT was shorter when the foreperiod lasted 500 ms than when it lasted 2500 ms, this result suggests that the excitability of the cortico-spinal structures is minimal when the subject is optimally ready to react. In experiment 2 (n = 10), the time-course of this decrement was further explored. With this aim, only the short foreperiod was used and the TMS was delivered either 500 ms, 333 ms, 167 ms or 0 ms before the response signal. Cortico-spinal excitability decreased during the first 333 ms and then remained stable until the occurrence of the response signal. In light of previous studies, the present results suggest that the decrement of cortico-spinal excitability during the short foreperiod reflects an adaptative mechanism which increases the sensitivity of the motor structures to the forthcoming voluntary command.

Multineuronal spike classification based on multisite electrode recording, whole-waveform analysis, and hierarchical clustering

We proposed here a method of multineuronal spike classification based on multisite electrode recording, whole-waveform analysis, and hierarchical clustering for studying correlated activities of adjacent neurons in nervous systems. Multineuronal spikes were recorded with a multisite electrode placed in the hippocampal pyramidal cell layer of anesthetized rats. If the impedance of each electrode site is relatively low and the distance between electrode sites is sufficiently small, a spike generated by a neuron is simultaneously recorded at multielectrode sites with different amplitudes. The covariance between the spike waveform at each electrode site and a template was calculated as a damping factor due to the volume conduction of the spike from the neuron to the electrode site. Calculated damping factors were vectorized and analyzed by hierarchical clustering using a multidimensional statistical test. Since a cluster of damping vectors was shown to correspond to an antidromically identified neuron, spikes of different neurons are classified by referring to the distributions of damping vectors. Errors in damping vector calculation due to partially overlapping spikes were minimized by successively subtracting preceding spikes from raw data. Clustering errors due to complex spike bursts (i,e., spikes with variable amplitudes) were avoided by detecting such bursts and then using only the first spike of a burst for clustering. These special procedures produced better cluster separation than conventional methods, and enabled multiple neuronal spikes to be classified automatically. Waveforms of classified spikes were well superimposed. We concluded that this method is particularly useful for separating the activities of adjacent neurons that fire partially overlapping spikes and/or complex spike bursts.

Involvement of the histaminergic system in renal sympathetic and cardiovascular responses to leptin and ghrelin.

Previous studies have demonstrated that histamine affects blood pressure (BP) in anesthetized rats. Here, we examined the effects of lateral cerebral ventricular (LCV) injection of various doses of histamine on renal sympathetic nerve activity (RSNA) and BP in anesthetized rats. LCV injection of a low dose of histamine (0.0001nmol) suppressed RSNA and BP. Conversely, a high dose of histamine (100nmol) elevated both RSNA and BP. Moreover, inhibiting effects of a low dose of histamine were eliminated by LCV pre-injection of thioperamide, an antagonist of histaminergic H3-receptor, and accelerating effects of a high dose of histamine were abolished by LCV pre-injection of diphenhydramine, an antagonist of histaminergic H1-receptor. Thus, these evidences suggest that central histamine affects RSNA and BP via histaminergic receptors. In addition, we examined a role for histaminergic system in cardiovascular modulators such as leptin and ghrelin. The LCV pre-injection of thioperamide clearly blocked suppressing effects of ghrelin on RSNA and BP. The LCV pre-injection of diphenhydramine also blocked elevating effects of leptin. Therefore, these results suggest that leptin and ghrelin might affect RSNA and BP by mediating central histaminegic H1- and H3-receptors, respectively.

Hyperexcitability-Associated Rapid Plasticity After a Focal Cerebral Ischemia

Background and Purpose— This article addresses how neuroplastic changes are initiated after an ischemic stroke. Methods— A focal cerebral ischemia was photochemically induced on the primary somatosensory cortex of rats, and in vivo electrophysiological recordings were performed on the peri-infarct cortex before and from 1 to 6 hours after the infarction. Results— Paired-pulse analysis of evoked field potentials to peripheral electrical stimuli showed statistically significant neuronal hyperexcitability that was associated with rapid expansion of receptive fields (146.1% at 1 hour and 553.6% at 6 hours) as early as 1 hour after the infarction (P <0.05). Current source density analysis revealed increased current sinks in cortical layer II/III. Conclusions— Our electrophysiological results showed, for the first time to our knowledge, rapid plastic changes in the peri-infarct cortex during the hyperacute stage of an ischemic stroke. Manipulation of this rapid plasticity may affect subsequent plastic changes.

In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz–10 kHz. The needles can penetrate into the whisker barrel area of a rats cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology.

Quantitative analysis of functional clustering of neurons in the macaque inferior temporal cortex.

Neurons with similar preferences for two-dimensional shapes of intermediate complexity cluster in area TE of the monkey inferior temporal cortex. To further characterize the functional structure of area TE, we quantitatively analyzed various aspects of the visual responses of closely located neurons by applying multiple single-unit recording techniques in anesthetized monkeys. Examination of the visual responses elicited with a large, predetermined set of visual stimuli confirmed previous findings that nearby neurons, on average, exhibited positively correlated preferences for a set of visual stimuli. Nearby neurons also tended to be similar in their receptive-field organization and contrast-polarity preference. In contrast, no correlation was found in the size tuning of neighboring neurons. Pooling or subtraction of activities between a pair of nearby neurons was shown to improve stimulus discriminability, if the neuron pair had positively or negatively correlated stimulus preferences, respectively. These results indicate that nearby TE neurons share some aspects of stimulus preference, but their response selectivity differ in other aspects. Both pooling and subtraction between nearby neurons can reduce across-trial response variability, if these decoding strategies are applied to appropriate neuronal pools.

Tracking Spike-Amplitude Changes to Improve the Quality of Multineuronal Data Analysis

During extracellular electrophysiological recording experiments, the waveform of neuronal spikes recorded from a single neuron often changes. These spike-waveform changes make single-neuron identification difficult, particularly when the activities of multiple neurons are simultaneously recorded with a multichannel microelectrode, such as a tetrode or a heptode. We have developed a tracking method of individual neurons despite their changing spike amplitudes. The method is based on a bottom-up hierarchical clustering algorithm that tracks each neurons spike cluster during temporally overlapping clustering periods. We evaluated this method by comparing spike sorting with and without cluster tracking of an identical series of multineuronal spikes recorded from monkey area-TE neurons responding to a set of visual stimuli. According to Shannons information theory, errors in spike-amplitude tracking reduce the expected value of the amount of information about a stimulus set that is transferred by the spike train of a cluster. In this study, cluster tracking significantly increased the expected value of the amount of information transferred by a spike train (p<0.01). Additionally, the stability of the stimulus preference and that of the cross-correlation between clusters improved significantly (p<0.000001). We conclude that cluster tracking improves the quality of multineuronal data analysis

Lasting effect of No on glutamate release in rat striatum revealed by continuous brain dialysis

THE effect of nitric oxide (NO) on glutamate release in the brain of freely moving rats was investigated using a new, high time-resolution microdialysis system. Coperfusion with veratridine (VER) and NO donors increased glutamate release above than that obtained with VER alone. When steady-state levels were regained after co-perfusion, perfusion of VER alone further potentiated glutamate release. The effect depended on the initial level of VER-induced glutamate release, and was maximum for intermediate glutamate levels. These results suggest that NO influences the glutamate release system by affecting the level of neural activity and that its effect lasts and increases when steady-state levels are regained in rat striatum.

Enlarged gold-tipped silicon microprobe arrays and signal compensation for multi-site electroretinogram recordings in the isolated carp retina.

In order to record multi-site electroretinogram (ERG) responses in isolated carp retinae, we utilized three-dimensional (3D), extracellular, 3.5-μm-diameter silicon (Si) probe arrays fabricated by the selective vapor-liquid-solid (VLS) growth method. Neural recordings with the Si microprobe exhibit low signal-to-noise (S/N) ratios of recorded responses due to the high-electrical-impedance characteristics of the small recording area at the probe tip. To increase the S/N ratio, we designed and fabricated enlarged gold (Au) tipped Si microprobes (10-μm-diameter Au tip and 3.5-μm-diameter probe body). In addition, we demonstrated that the signal attenuation and phase delay of ERG responses recorded via the Si probe can be compensated by the inverse filtering method. We conclude that the reduction of probe impedance and the compensation of recorded signals are useful approaches to obtain distortion-free recording of neural signals with high-impedance microelectrodes.