Hiroshi Nakahama

Firing properties of two types of nucleus raphe dorsalia neurons during the sleep-walking cycle and their responses to sensory stimuli

Spontaneous activity of the nucleus raphe dorsalis (NRD) neurons during the sleep-waking cycle and effects of sensory stimuli upon NRD neurons were studied in cats. Seventy-one neurons recorded within the NRD were classified into two groups with the use of the coefficient of variation of firing intervals during waking (W): 41 regularly firing (clock-like) and 30 irregularly firing (non-clock-like) neurons. The majority of clock-like and one-third of non-clock-like neurons showed a decrease in their firing rate during slow-wave sleep (SWS) compared with W. All neurons of both types displayed their lowest level of activity during paradoxical sleep. During the late phase of SWS, many clock-like neurons reduced their firing prior to the occurrence of pontogeniculo-occipital waves, whereas non-clock-like neurons did not show such a specific property. Clock-like neurons were totally unresponsive to nociceptive and non-nociceptive somesthetic stimuli, while about half of the non-clock-like neurons were driven by these stimuli. Half of the clock-like and one-third of the non-clock-like neurons were driven by click stimulation, and the majority of them showed an excitatory response. Some of the clock-like and non-clock-like neurons exhibited inhibitory and excitatory response to flash stimulation, respectively. The results of this experiment show that two types of neurons do exist in the NRD and suggest that they play a functionally different role in the brain.

Arthritis induced in cat by sodium urate: a possible animal model for tonic pain

Abstract An attempt has been made to determine whether cats rendered arthritic by the injection of monosodium urate (MSU) crystals (rod‐shaped 40–130 &mgr;m length) into one knee joint capsule can be used as an animal model of tonic (chronic) pain. A limp and a decrease in body weight supported by the injected hind legs paw occurred approximately l h after the MSU (20 mg) injection, reached a maximum at 2–3 h, and lasted for more than 6 h before a gradual return to pre‐injection levels. They were diminished by systemic administration and local (the dorsal part of the nucleus raphe dorsalis) application of morphine, this effect being blocked by naloxone. This suggests that the limping and the paw pressure decrease are the reflexion of pain. It is suggested that the animal model of the MSU‐induced arthritis is useful for the study of tonic pain.

Evaluation of the analgesic effects of capsaicin using a new rat model for tonic pain.

An animal model for tonic pain has been produced by means of injecting monosodium urate crystals into a knee joint of rat hind paws in order to evaluate the analgesic effects of various drugs and analgesic methods and to elucidate the physiology of tonic pain. This model allows for stable and long-term behavioural changes due to tonic pain followed by complete recovery without tissue damages. It is advantageous in allowing for objective and quantitative evaluation of the effects of analgesics and should prove useful in research on pain and the development of pain therapy techniques. Using this model, the analgesic effects of capsaicin was evaluated when administered to the neonatal rat or locally to peripheral nerves. In both cases, significant analgesic effects were obtained.

Markov-dependency and spectral analyses on spike-counts in mesencephalic reticular neurons during sleep and attentive states

Spontaneous activities of the mesencephalic reticular formation (MRF) neurons of head-restrained cats were recorded to investigate their dynamic properties during sleep and waking. The Markov-dependency and spectral analyses were performed on the time series of counts converted from the MRF spike-train. During slow-wave sleep (SWS), MRF neurons fired with low Markovian properties and had a similar spectral-density curve as white noise; during paradoxical sleep (PS), their firing pattern showed high Markovian properties owing to low-frequency fluctuations, with spectral densities inversely proportional to frequency (the l/f spectrum). During the attentive state of bird watching (BW), intermediate Markovian properties were observed. These results confirmed both the rest theory of SWS and the activation of the brain during PS from the viewpoint of dynamic information-processing. Furthermore, the activation of the brain during PS may be greater than in BW.

Markov Process of Maintained Impulse Activity in Central Single Neurons

To clarify the stochast properties of the maintained impulse activity of the central nervous system, we proposed a measure of statistical dependency on the basis of Shannons entropy. This measure could provide the Markov properties of the neural impulse sequences, representing the necessary and sufficient condition for the statistical dependence. The order of Markov process of the sequence is determined by the conditional entropy which is derived from the joint entropy. Here the joint entropy in the case of Gaussian process is directly related with the covariance matrix which is substituted for the matrix of the serial correlation coefficients. Therefore the condition to determine the order of Markov process is obtained by the equation of the matrices of the serial correlation coefficients. The order of Markov process of the neural impulse sequences recorded from the mesencephalic reticular formation (MRF), red nucleus (RN), and lateral geniculate nucleus (LGN) neurons has been estimated. The maintained impulse activity of the MRF and RN neurons had from the 2-nd to 4-th order Markov property, while that of the LGN had no Markov property, in the consecutive impulse sequences.

Antinociceptive action of morphine and pentazocine on unit activity in the nucleus centralis lateralis, nucleus ventralis lateralis and nearby structures of the cat

Abstract Single neuronal activity has been recorded extracellularly from the nucleus centralis lateralis (CL), ventralis lateralis (VL) and medialis dorsalis (MD) of the cat thalamus. The majority of the CL, VL and MD neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intra‐arterial injection of bradykinin. The nociceptive neurons were also driven by non‐nociceptive stimulation such as tap of deep tissues, bending hairs with an air‐puff and/or joint rotation, and their receptive fields were large. After intravenous administration of either morphine or pentazocine, most nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non‐nociceptive stimuli. This suggests that morphine and pentazocine have a specific antinociceptive action on these nociceptive neurons, Intravenous naloxone reversed the antinociceptive action of morphine, but failed to reduce the action of pentazocine. This differentiation has an important functional significance.

A statistical analysis of spontaneous activity of central single neurons

Abstract Spontaneous activity of the single neurons of the lateral geniculate body (LG), the ventrobasal complex (VB; modality, skin), the red nucleus (RN), the thalamic reticular formation (TRF), and the midbrain reticular formation (MRF) in cats were studied in terms of a statistical analysis in the absence of any intentional and specific sensory stimuli. The mean interval, standard deviation and coefficient of variation of most of the neurons examined were larger in sleep than in arousal. Serial correlation coefficients of interval sequence of spontaneous impulses were larger in positive value during the arousal state than in the sleep state for a given neuron, although the serial correlation coefficients obtained during the sleep state showed high values in RN, TRF, and MRF neurons, and low values in LG and VB neurons. The serial correlation coefficients of at least the first several orders in RN, TRF, and MRF were positive, while those in LG and VB were negative or positive.

Analgesic effects of serotonin microinjection into nucleus raphe magnus and nucleus raphe dorsalis evaluated by the monosodium urate (MSU) tonic pain model in the rat

The effects of 5-hydroxytryptamine (5-HT) microinjection into the nucleus raphe magnus (NRM) and the nucleus raphe dorsalis (NRD) on tonic pain were studied using the monosodium urate (MSU) tonic pain model in the rat. For the NRM, 5-HT microinjection produced significant analgesic effects, which were antagonized by systemic naloxone administration and also by subsequent microinjection of naloxone into the NRM. For the NRD, systemic naloxone administration did not antagonize these analgesic effects, although 5-HT microinjection produced significant analgesic effects. Therefore, as far as tonic pain is concerned, it was suggested that neural transmission mediated by 5-HT in the NRM and NRD plays an antinociceptive action, but via different neural mechanisms.

Regularity of the spontaneous discharge of neurons in the nucleus raphe dorsalis of the cat

Impulse discharges were recorded from 43 neurons in the nucleus raphe dorsalis of the cat. Of these neurons examine for spontaneous activity, 23 fired in remarkable regular rhythm (clock-like neurons); 18 fired irregularly (non-clock-like neurons); and 2 fired with an unclassified pattern. Almost all clock-like neurons were unresponsive to any kind of peripheral somatic stimuli, while the majority of non-clock-like neurons were excited by both nociceptive and non-nociceptive stimuli or by non-nociceptive stimuli. The somatic receptive fields were large, spanning the entire body.

Slow fluctuations of single unit activities of hippocampal and thalamic neurons in cats. I. Relation to natural sleep and alert states

Spontaneous unit discharges during the natural sleep-wakefulness cycle in two different neuronal groups, the hippocampal pyramidal cells and thalamic ventrobasal neurons, have been analyzed. The results show that both neurons fire with white-noise-like fluctuations during the slow-wave sleep, and with slow fluctuations with power spectral densities inversely proportional to the frequency in the frequency range of 0.02-1.0 Hz, during the paradoxical sleep. This confirms that the characteristics of fluctuations in neuronal activities of the mesencephalic reticular formation observed in our previous study are more general phenomena in the cats brain. Partly similar behavior of spectral densities is also observed during the alert state. These observations are quantitatively confirmed by the statistical time series analysis of the spike density processes of spontaneous activities.