Shinya S. Suzuki

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.

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.

Immunohistochemical analysis on the role of adenosine A1 receptors in epilepsy

Adenosine has an anticonvulsant effect in various models of epilepsy. This effect appears to be mediated through the activation of adenosine A1 receptors (A1Rs). We immunohistochemically investigated the changes of A1Rs expression in kainate-treated and hippocampus-kindled rats as chronic models of epilepsy. In the normal hippocampus, a predominant expression of A1Rs was detected in the CA2/CA3a field. The A1Rs immunoreactivity in this field began to decline drastically approximately 4 weeks after kainate treatment and remained minimal 8 weeks after treatment. In the hippocampus-kindled animals, A1Rs expression was minimal in the stimulated side but remained high in the nonstimulated side. The reduced expression of A1Rs in the CA2/CA3a field may be related to chronic epileptogenesis.

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.

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.

Effect of long-term potentiation induction on gamma-band electroencephalograms in prefrontal cortex following stimulation of rat hippocampus in vivo

We examined whether long-term potentiation (LTP) affects cortical gamma-band electroencephalograms (EEG) in the hippocampo-prefrontal cortex (PFC) pathway of anesthetized rats. The LTP induction increased the evoked PFC gamma-band EEG power (40-100 Hz) to 120-135% at 500-700 ms after test stimulation. A simple increment of stimulus intensity, instead of LTP induction, did not reveal this evoked increase. Neither LTP induction nor the intensity increment changed significantly the magnitude of an evoked decrease at around 100 ms or the spontaneous prestimulation gamma-band power. These results indicate that LTP in PFC specifically increases the evoked gamma-band EEG power, which may reflect a phasic mode of plastic neurotransmission through the hippocampo-PFC pathway in vivo.

A choice reaction-time task in the rat: A new model using air-puff stimuli and lever-release responses

We have developed a two-lever choice reaction-time (RT) task to investigate the behavioral and neural mechanisms of stimulus-response compatibility in rats. In the task, the rat pressed two levers with its forepaws during the preparation period of each trial, and then quickly responded to an air-puff stimulus on its left or right forepaw by releasing the lever on the same side (compatible condition) or the opposite side (incompatible condition) of the stimulus. Twenty rats successfully learned the task in both the compatible and incompatible conditions. Two stimulus-response compatibility effects were observed: the RT was shorter and the error rate was lower in the compatible condition than in the incompatible condition. The trial sequence also affected the results and a speed-accuracy tradeoff was observed. These results are consistent with those reported for human RT tasks. Furthermore, a lesion in the forepaw-sensorimotor cortex caused increases in the RTs for stimulus detection and/or response movement with the contralateral forepaw, suggesting that the task was mediated by this brain area. We conclude that this instrumental task for rats can be regarded as a model for human RT tasks and can be used to investigate the neural basis of the compatibility effects.

Epileptiform discharges and neuronal plasticity in the acute peri-infarct cortex of rats

Abstract While the peri-infarct cortex is thought to be responsible for functional recovery, the site is also a strong candidate for post-stroke seizures. Since it is crucial to identify the conditions when the site is changed with such beneficial or detrimental results, the peri-infarct changes were investigated before and just after inducing a focal infarct on rat cortex. The receptive fields in the peri-infarct cortex began to increase a few hours after the infarct, and reached a statistical significance at 6 hours (Dunnett post hoc tests; p<0·05). In temporal association with these changes, EEG in the peri-infarct cortex showed epileptiform activities containing large-amplitude spike-and-wave discharges. The gross amplitude, peak-to-peak amplitude and burst frequency showed statistically significant increases within 4 hours, in comparison to those of the controls (Dunnett post hoc tests; p<0·05). FFT power spectrum analyses showed a distinct increase in ∼25 Hz frequency bands in the post-stroke groups. The homogeneous area of the contralateral hemisphere in the infarct group, in contrast, did not show such plastic or excitability changes. This study demonstrated, for the first time, that the peri-infarct cortex acquires the characteristics of potential epileptogenesis and functional recovery within hours of a stroke.

Sensitization of glutamate release and N-methyl-D-aspartate receptor response by transient dopamine pretreatment in prefrontal cortex of rats.

We studied biochemically the effect of transient dopamine pretreatment on the regulation of glutamate transmission in medial prefrontal cortex of rats in vivo and in vitro. Aversive stimuli transiently increased the glutamate concentration and its repetition reduced the response in the medial prefrontal microdialysate of freely moving rats. The rate of habituation obeyed linear regression. The medial prefrontal intracellular calcium response to repetitive N-methyl-D-aspartate perfusion showed linearly regressive desensitization in fluorescence videomicroscopy of the fura-2 stained slice in vitro. Transient dopamine treatment 10-20 min prior to repetition restored both decreased responses in a linearly regressive manner, also indicating that their decrease was not due to fatigue. These findings suggest that the effect of transient dopamine pretreatment continues redundantly to sensitize/resensitize subsequent pre- and postsynaptic prefrontal glutamate transmission in an orderly manner.