Freely-moving Cats Research Articles

Adaptability of Kinetic Parameters to a Narrow Speed Range in Healthy Free-Moving Cats

Ground reaction force and impulse measurement is an established method for assessing the physical condition and efficacy of treatment for some animals. The primary aim of this study was to quantify the kinetic parameters of the limbs of healthy cats at different speeds. The second aim was to determine the explicit relationship between the kinetic parameters and speed. Peak vertical force (PVF), vertical impulse (VI), stance phase duration (SPD), and paw contact area (PCA) of each limb (forelimb, F; hindlimb, H) of seven clinically healthy, client-owned cats were recorded in the speed interval of 0.5–2.5 m/s. The cats were encouraged to pass by a pressure-sensitive walkway with different speeds. The results revealed that there were no significant differences in any of the tested parameters between the left and right forelimbs and the left and right hindlimbs. Means and regression formulas of the kinetic parameters with speed were obtained. It was evident that PVF-F and PVF-H increased linearly with speed, while VI-F and VI-H decreased exponentially. SPD-F was practically equal to SPD-H and exponentially decreased with speed. PCA-F increased linearly with speed, and PCA-H was almost invariable. Pressure-sensitive walkway is a suitable and convenient equipment for assessing the kinetic parameters of cats. Variation of these kinetic parameters with speed can be explained by the functional difference for forelimb-dominant and hindlimb-driven.

Ascending Reticular Activating System of the Brain

There were two stages in the history of the studies on ascending reticular activating system of the brain (ARAS). The first stage began with the ARAS discovery by Magoun and Moruzzi and the following investigations using the methods of stimulation and lesion at that time mainly in acute cats. These studies led to the hypothesis of a “diffuse” and “unspecific” ARAS of the brain stem. The second stage was associated with using more precise neurophysiological and histochemical methods mainly in chronically operated free-moving cats and rats. By 2010, the idea of the ARAS as an organized hierarchy of the cerebral “waking centers” distributed along the entire cerebral axis and releasing all the known neuromediators of low molecular weight together with the most important neuropeptides was formulated. To date, the aforementioned hypothesis has been revised again. The glutamatergic activating system has been discovered and described in detail. Presumably, this system is responsible for the appearance of electroencephalogram (EEG) arousal reaction and maintenance of the neocortex in the state of tonic depolarization during wakefulness and rapid eye movement (REM) sleep. Its destruction results in a deep comatose-like state. At the same time, the activity of all other “waking centers” is probably the result of the cortical activation.

Response properties of neurons in the cat’s putamen during auditory discrimination

The striatum integrates diverse convergent input and plays a critical role in the goal-directed behaviors. To date, the auditory functions of striatum are less studied. Recently, it was demonstrated that auditory cortico-striatal projections influence behavioral performance during a frequency discrimination task. To reveal the functions of striatal neurons in auditory discrimination, we recorded the single-unit spike activities in the putamen (dorsal striatum) of free-moving cats while performing a Go/No-go task to discriminate the sounds with different modulation rates (12.5Hz vs. 50Hz) or envelopes (damped vs. ramped). We found that the putamen neurons can be broadly divided into four groups according to their contributions to sound discrimination. First, 40% of neurons showed vigorous responses synchronized to the sound envelope, and could precisely discriminate different sounds. Second, 18% of neurons showed a high preference of ramped to damped sounds, but no preference for modulation rate. They could only discriminate the change of sound envelope. Third, 27% of neurons rapidly adapted to the sound stimuli, had no ability of sound discrimination. Fourth, 15% of neurons discriminated the sounds dependent on the reward-prediction. Comparing to passively listening condition, the activities of putamen neurons were significantly enhanced by the engagement of the auditory tasks, but not modulated by the cat’s behavioral choice. The coexistence of multiple types of neurons suggests that the putamen is involved in the transformation from auditory representation to stimulus-reward association.

Correlation between neural discharges in cat primary auditory cortex and tone-detection behaviors

Understanding the physiological role of the auditory cortex (AC) in acoustic perception is an essential issue in auditory neuroscience. By comparing sound discrimination behaviors in animals before and after AC lesion, many studies have demonstrated that AC is necessary for the perceptual process of human vowels and animal vocalizations, but is not necessary to discriminate simple acoustic parameters such as sound onset, intensity and duration. Because a lesion study cannot fully reveal the function of AC under normal conditions, in this study, we combined electrophysiological recording and psychophysical experiments on the same animal to investigate whether AC is involved in a simple auditory task. We recorded the neural activities of the primary auditory cortex (A1) using implanted electrodes, while freely-moving cats performed a tone-detection task in which they were required to lick a metal tube to obtain a food reward after hearing a tone pip. The performance of the cats’ behavioral response increased with the increase of tone intensity, and the neural activities of A1 covaried with the behavioral performance. Also, whether the tone-detection behavior was interfered by a wideband noise was dependent on whether the tone-evoked neural response was masked by the noise-evoked response. Our results did not support that A1 neurons directly associate with the cat's behavioral decision; instead, they may mainly generate a neural representation of stimulus amplitude for further processing to determine whether a tone occurred or not.

Brainstem neurons responsible for postural, masseter or pharyngeal muscle atonia during paradoxical sleep in freely-moving cats.

In this mini review, we summarize our findings regarding the brainstem neurons responsible for the postural, masseter, or pharyngeal muscle atonia observed during paradoxical sleep (PS) in freely moving cats. Both the pons and medulla contain neurons showing tonic activation selective to PS and atonia, referred to as PS/atonia-on-neurons. The PS/atonia-on neurons, characterized by their most slow conducting property and located in the peri-locus coeruleus alpha (peri-LCa) and adjacent LCa of the mediodorsal pontine tegmentum, play a critical executive role in the somatic and orofacial muscle atonia observed during PS. Slow conducting medullary PS/atonia-on neurons located in the nuclei reticularis magnocellularis (Mc) and parvocellularis (Pc) may play a critical executive role in the generation of, respectively, antigravity or orofacial muscle atonia during PS. In addition, either tonic or phasic cessation of activity of medullary serotonergic neurons may play an important role in the atonia of genioglossus muscles during PS via a mechanism of disfacilitation.

Neural Responses in the Primary Auditory Cortex of Freely Behaving Cats While Discriminating Fast and Slow Click-Trains

Repeated acoustic events are ubiquitous temporal features of natural sounds. To reveal the neural representation of the sound repetition rate, a number of electrophysiological studies have been conducted on various mammals and it has been proposed that both the spike-time and firing rate of primary auditory cortex (A1) neurons encode the repetition rate. However, previous studies rarely examined how the experimental animals perceive the difference in the sound repetition rate, and a caveat to these experiments is that they compared physiological data obtained from animals with psychophysical data obtained from humans. In this study, for the first time, we directly investigated acoustic perception and the underlying neural mechanisms in the same experimental animal by examining spike activities in the A1 of free-moving cats while performing a Go/No-go task to discriminate the click-trains at different repetition rates (12.5–200 Hz). As reported by previous studies on passively listening animals, A1 neurons showed both synchronized and non-synchronized responses to the click-trains. We further found that the neural performance estimated from the precise temporal information of synchronized units was good enough to distinguish all 16.7–200 Hz from the 12.5 Hz repetition rate; however, the cats showed declining behavioral performance with the decrease of the target repetition rate, indicating an increase of difficulty in discriminating two slower click-trains. Such behavioral performance was well explained by the firing rate of some synchronized and non-synchronized units. Trial-by-trial analysis indicated that A1 activity was not affected by the cat's judgment of behavioral response. Our results suggest that the main function of A1 is to effectively represent temporal signals using both spike timing and firing rate, while the cats may read out the rate-coding information to perform the task in this experiment.

Comparing cortical neural responses to tone stimuli under the passively and actively listening conditions of free-moving cats

Comparing cortical neural responses to tone stimuli under the passively and actively listening conditions of free-moving cats

Sleep‐wakefulness effects after microinjections of hypocretin 1 (orexin A) in cholinoceptive areas of the cat oral pontine tegmentum

Hypocretinergic/orexinergic neurons, which are known to be implicated in narcolepsy, project to the pontine tegmentum areas involved in the control of rapid eye movement (REM) sleep. Here, we report the effects on sleep-wakefulness produced by low-volume microinjections of hypocretin (Hcrt)1 (20-30 nL, 100, 500 and 1000 microm) and carbachol (20-30 nL, 0.1 m) delivered in two areas of the oral pontine tegmentum of free-moving cats with electrodes for chronic sleep recordings: in the dorsal oral pontine tegmentum (DOPT) and in the ventral part of the oral pontine reticular nucleus (vRPO). Carbachol in the DOPT produced dissociate polygraphic states, with some but not all REM sleep signs. In contrast, carbachol in the vRPO produced a shift with short latency from wakefulness (W) to REM sleep with all of its polygraphic and behavioral signs. Hcrt-1 in the DOPT increased W and decreased both slow-wave sleep (SWS) and REM sleep during the first 3 h post-drug. The same doses of Hcr-1 in the vRPO produced a significant suppression of REM sleep without a definitive trend for changes in the other states. Both groups showed significant decreases in the number of transitions from SWS to REM sleep. Thus, Hcrt-1 produced distinct effects in cholinoceptive areas of the oral pontine tegmentum; in the DOPT it promoted W, suppressed SWS and probably defacilitated REM sleep, and in the vRPO it directly inhibited REM sleep. Hypocretinergic/orexinergic signaling is lost in narcoleptics and this absence would mean that pontine defacilitation/inhibition of REM sleep would also be absent, explaining why these patients can fall directly into REM sleep from W.

Effect of Injury to the Dorsal Funiculus of the Thoracic Spinal Cord on Micturition in Decerebrate and Freely-Moving Cats

Bladder sensation is transmitted both via the spinothalamic tract in the lateral funiculus and the dorsal system in the dorsal funiculus. We transected the dorsal funiculus in 10 female cats to clarify the functional roles of these two ascending pathways. The dorsal funiculus was transected at T10 in 5 decerebrate and 5 freely-moving cats, and micturition parameters were compared before and after transection. Transection of the dorsal funiculus did not affect any of the parameters of reflex micturition in the 5 decerebrate cats. Within 1 week after transection, 4 of the 5 freely-moving cats used the normal micturition posture, but the remaining one performed micturition in a prone position as if she had lost micturition sensation. All 5 cats urinated with a normal micturition posture by 2 weeks after transection. The mean single voided volume was decreased transiently up to 1 week, but returned to normal by 2 weeks after transection. None of the 5 cats had any residual urine before and after transection. Both the ascending and descending limbs of the micturition reflex pass through the lateral funiculus. Bladder sensation is transmitted both via the spinothalamic tract coursing in the lateral funiculus and the dorsal system in the dorsal funiculus. The dorsal system may play a major role in the transmission of bladder sensation to the cerebral cortex, but may not be essential.

Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat

In light of evidence implicating dopamine in the pathophysiology of attention deficit disorder and schizophrenia, diseases involving attentional or sensory processing abnormalities, it was of interest to determine whether and how dopamine neurons in the ventral tegmental area respond to sensory stimuli. The single-unit responses of ventral tegmental dopamine neurons were recorded in freely-moving cats during the presentation of brief, non-conditioned auditory and visual stimuli. Both auditory and visual stimuli produced neuronal excitation, involving a greater than 5-fold increase in the probability of burst firing followed by a period of burst inhibition. The burst nature of the single-unit response suggests that sensory-induced dopamine release at target sites was disproportionally large relative to the discharge frequency. While characteristics of the dopaminergic sensory response were similar for auditory and visual stimuli, the response latency was longer for visual stimuli. The results demonstrate that dopamine neurons in the ventral tegmental area, the site of origin for mesolimbocortical dopamine neurons, are reliably activated by non-conditioned auditory and visual stimuli.

Repeated penicillin-induced amygdala epileptic focus in freely moving cats. EEG, polysomnographic (23-h recording), and brain mapping study.

The effect of repeated Na-penicillin (PCN) microinjections in the temporal lobe amygdala (AM) of free-moving cats was investigated in order to establish if kindling epileptogenesis is possible with this procedure. The cortical propagation of the PCN-induced post-discharge in AM and the sequence of behavioral changes induced by PCN were similar to those of AM electrical kindling. Nevertheless, the epileptogenic effect of PCN had a different evolution from that of electrical kindling, since some PCN habituation was observed after several doses. Repeated microinjections of PCN did not produce lasting alterations in sleep onset and organization. The only mild changes recorded in the 23 h following PCN microinjections were an increased latency of the first rapid eye movement (REM) sleep episode, a SWS II total time and percentage increase, and, with the highest PCN doses, a not very significant diminution of REM sleep total time. Another finding was the occurrence of REM sleep ponto-geniculo-occipital (PGO) waves, coinciding with a depression of the frequency and amplitude of interictal amygdaloid and cortical spikes. The results showed that a microinjection of PCN in the AM produced a reliable model of interictal spikes, paroxysms and generalized convulsive seizures. Nevertheless, long lasting kindling effect was not observed.

Measurement of Extracellular Calcium Ions within the Hypothalamus of the Freely-Moving Cat: A Novel Approach

Abstract In order to investigate the kinetics of calcium ion (Ca++) activity within the hypothalamus by high performance liquid chromatography, standard push-pull guide cannulae were implanted stereotaxically above the hypothalamus of the cat. Following post-operative recovery, an isotonic artificial cerebrospinal fluid (ACSF) was perfused in the site at a rate of 25 ul/min over successive intervals of 5.0 min. In the mid-point of a sequence of repeated push-pull perfusions, verapamil (4.0 ug/ul) was added to the perfusate. Samples collected from the hypothalamus of the freely-moving cat were analyzed for calcium concentration by an HPLC conductivity detector. The results showed that verapamil perfused within the hypothalamus of the cat caused an efflux of calcium ion into the perfusate which was detected by HPLC. This study proposes a new approach to precisely determine the calcium concentration in extracellular fluid in awake freely-moving animals.

Buspirone decreases the activity of serotonin-containing neurons in the dorsal raphe in freely-moving cats

Buspirone, a non-benzodiazepine anxiolytic agent, produced a dose-dependent decrease in the activity of serotonin-containing neurons in the dorsal raphe nucleus of freely-moving cats. The response ranged from no significant change at doses of 0.05 mg/kg to a nearly total suppression of activity at 1 mg/kg These data suggest that the anxiolytic properties of buspirone may be mediated, at least part, by an action on neurons in the dorsal raphe.

Modulation of paroxysmal activity in the hippocampus by caudate stimulation in the chronic cat

Afterdischarges in the dorsal hippocampus (HADs) were studied in freely-moving cats with implanted electrodes following threshold stimulation of the mirror-image point on the contralateral side. Marked inhibition, similar so that seen in acute animals, was observed when the test stimulation was immediately preceded by a conditioning stimulus applied to the caudate nucleus. The inhibitory effect appeared to be larger in these chronic animals than in the acute preparations previously studied, probably because of the total absence of anaesthesia during the recording session. When the HAD is preceded by caudate stimulation, its duration can be graduated by the intensity of the hippocampal test stimulation. The results are discussed in terms of a possible modulation induced directly or indirectly by the caudate nucleus in the hippocampus, which reacts in a gradual manner to the excitatory volley.

Unit activity in the dorsal raphe in freely-moving cats: Effects of monoamine oxidase inhibitors

Two commonly used monoamine oxidase inhibitors, tranylcypromine and pargyline, produced dose-dependent decreases in the activity of serotonin-containing neurons in the dorsal raphe in awake, freely-moving cats. The onset of the suppression of unit activity occurred within 15–20 min after administration of drug and persisted for 6–16 hr, depending upon dose. Parallel neurochemical studies revealed that serotonin in the brain was significantly increased following inhibition of monoamine oxidase, and that concentrations of serotonin were still significantly elevated after unit activity in the raphe had returned to baseline levels. These data suggest that autoreceptors on neurons of the dorsal raphe may become tolerant following prolonged exposure to large concentrations of serotonin.

Cortical visual evoked potentials during the sleep-wakefulness cycle in the freely moving cat. A dynamic study.

The dynamic features of visual evoked potentials, elicited by a light emitting diode chronically implanted in the frontal sinus of the freely moving cat, were studied during sleep stages by means of calculation of the power spectra of the EEG prior to the stimulus and the poststimulus EEG which contain the single evoked potential. The statistical analysis between mean frequencies from both EEG prior to the stimulus and single evoked potential, within each sleep stage, showed that the main changes occurred during slow sleep, with a significant increase in the percentage of the alpha band. These results are interpreted as a partial desynchronization evoked by the visual stimulation during the synchronized phase of sleep.

Effect of nizofenone on pyramidal response, electrocorticogram and regional cerebral blood flow following recirculation after complete global brain ischemia in cats

Effect of nizofenone on pyramidal response (PR), electrocorticogram (ECoG) and regional cerebral blood flow (rCBF) following recirculation after complete global brain ischemia was compared with that of pentobarbital in gallamine-immobilized cats. The basilar artery and the branches of both carotid arteries (superior thyroid artery, dorsal muscular branch, internal carotid artery, occipital artery and ascending pharyngeal artery) were all ligated. The cats were subjected to complete brain ischemia by occluding both common carotid arteries for 45 min, followed by 180 min recirculation. rCBF of the cortex (suprasylvian gyrus) and the internal capsule was monitored by the hydrogen clearance method. Blood gases were regulated within a range determined previously in freely-moving cats throughout the experiment. Nizofenone (1 mg/kg, i.v.) facilitated the recovery of PR and ECoG, and it inhibited the phenomenon of secondary suppression evidenced by interruption and reversion of the recovery process. rCBF showed good recovery throughout the recirculation period. Pentobarbital (20 mg/kg, i.v.) facilitated the recovery of PR during the early period of recirculation, but secondary suppression of PR, associated with the decline of rCBF, was evident. These results suggest that the ameliorative effect of nizofenone on the recovery of neuronal functions is due to its ability to protect neurons against ischemic anoxia and to prevent interruption of postischemic circulation, and also the good recovery of rCBF is due to its ability to protect vasculature against ischemic anoxia.

Raphe unit activity in freely moving cats: Effects of quipazine

Quipazine produced a dose-dependent decrease in the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of freely-moving cats. This ranged from a 10% decrease at 0.5 mg/kg, (i.p.), to a virtually complete depression of activity at 5.0 mg/kg. The effects of quipazine on raphe units occurred with a short latency (5–10 min) and its duration of action was dose-dependent and lasted from 1 to 6 hr. The degree of depression of raphe unit activity was directly related to the frequency of occurrence of a number of behaviors such as limb flicking and abortive grooming. There was a close temporal correlation between the depression of raphe unit activity and the occurrence of these behaviors. These data reveal that quipazine produces behavioral and raphe unit changes similar to those observed after administration of hallucinogens with an indole nucleus.

Subcortical influences upon prefrontal cortex of the cat

Extracellular unit recordings were obtained from the prefrontal cortex (CPF) of free-moving cats with the head fixed. The prevailing effect produced by electrical stimulation of dorsal amygdala (AD) and N. medialis dorsalis thalami (DM) was a decrease in the spontaneous activity of CPF neurons, while lateral hypothalamus (HL) stimulation produced an increase. Concurrent electrical stimulation of HL and DM, and HL and AD produces suppression of the effect induced by HL single stimulation. Basal amygdala (AB) and DM simultaneous stimulation produces suppression of DM single stimulation.

Sleep elicited by olfactory tubercle stimulation and the effect of atropine

The effects of high-frequency olfactory tubercle (TbOf) stimulations were studied on the EEG and behaviour of freely-moving cats. The results were as follows: (1) TbOf stimulation elicited sleep similar in every respect to physiological sleep; (2) statistical evaluation of the results showed that primarily the appearance and maintenance of slow wave sleep was facilitated by the stimulations. Stimulations during paradoxical sleep had no effect, but they did promote the recurrence of slow wave sleep after the paradoxical sleep. The effect of stimulations during wakefulness depended on the on-going activity; (3) TbOf stimulation brought about synchronization, which was characterized by a similar arousal threshold as for physiological sleep; and (4) atropine treatment prevented the behavioural effects and did not influence the EEG effects of the stimulations.