W.R. Klemm

EEG and multiple-unit activity in limbic and motor systems during movement and immobility ☆

Abstract Electrographic activity was recorded from chronically implanted electrodes generally in the caudate nucleus, septum, hippocampus, and midbrain and medullary levels of the brain stem reticular formation (BSRF) of rabbits in order to assess the effects of movements and immobility. Hippocampal theta rhythms were triggered during movements of any sort or during phasic increases in muscle electrical activity. Coinciding with or preceding the theta onset were phasic increases of multiple-unit activity in the BSRF. Injection of tranquilizer simultaneously reduced movements, abolished theta rhythm, and selectively depressed BSRF units. These specific electrographic correlates of muscle activity were not observed in the caudate, septum, or other telencephalic brain structures from which recordings were derived. Transient theta and increased BSRF activity also occurred during the immobility reflex (animal hypnosis) when the tonic muscle relaxation and immobility were phasically interrupted by mild sensory stimulation. The motor-associated phasic increases in BSRF multiple-unit activity were superimposed upon a tonic unit activity increase in the medullary reticular formation, not seen elsewhere, that was characteristic of the reflex.

Physiological and behavioral significance of hippocampal rhythmic, slow activity (“theta rhythm”)

This review identifies some of the conflicts among currently popular theories on the significance of hippocampal rhythmic, slow activity (RSA). The review develops the rationale for a dualistic hypothesis in which RSA per se is regarded as having a different meaning from its frequency shifts. The hypothesis holds that RSA is part of an over-all adaptive “readiness response” to biologically significant stimuli that trigger responses in the brainstem reticular formation (BSRF). Specific frequency content of RSA, including shifts to low-voltage desynchrony, reflects the input and output processing reactions performed by the hippocampus as it participates in the brains response to stimulation. Specifically, RSA frequency shifts reflect the underlying chemical and electrical phenomena that are at least partially involved in regulating the different behaviors with which RSA has been correlated. Previous research has been largely devoted to correlating RSA with various functions and behavior. Correlative data alone cannot indicate whether RSA is a necessary or sufficient condition for occurrence of its correlated behavior. A basic merit of the dualistic hypothesis is that it fosters thinking and research strategies along heretofore unexploited directions, which could create the necessary data base for a more precise concept of RSA significance. This analysis includes suggestions of a general approach for testing the validity of the dualistic hypothesis.

Evidence for a cholinergic role in haloperidol-induced catalepsy

Experiments in mice tested previous evidence that activation of cholinergic systems promotes catalepsy and that cholinergic mechanisms need to be intact for full expression of neuroleptic-induced catalepsy. Large doses of the cholinomimetic, pilocarpine, could induce catalepsy when peripheral cholinergic receptors were blocked. Low doses of pilocarpine caused a pronounced enhancement of the catalepsy that was induced by the dopaminergic blocker, haloperidol. A muscarinic receptor blocker, atropine, disrupted haloperidol-induced catalepsy. Intracranial injection of an acetylcholine-synthesis inhibitor, hemicholinium, prevented the catalepsy that is usually induced by haloperidol. These findings suggest the hypothesis that the catalepsy that is produced by neuroleptics such as haloperidol is actually mediated by intrinsic central cholinergic systems. Alternatively, activation of central cholinergic systems could promote catalepsy by suppression of dopaminergic systems.

Ethanol-induced regional and dose-response differences in multiple-unit activity in rabbits.

Multiple-unit activity (MUA), recorded simultaneously from many brain areas, was used to detect the existence and location of ‘target sites’ for ethanol action in rabbits with chronically implanted electrodes in 14 areas. Each of 12 rabbits received intraperitoneal injection of 300, 600, 900, and 1200 mg/kg of 20% ETOH and a saline control injection given in random order with at least a 4-day interval between injections. Large amounts of MUA data, recorded continuously for a 2-min pre-injection control period and a 15-min post-injection period, were quantified by a sensitive and unique technique. MUA changes did not correlate with alcohol-induced changes in the corresponding EEG for the same locus. Whereas visual inspection of the EEG did not disclose any regional differences in response to ethanol, both temporal and topographical differences in ethanol effect on MUA were observed. There were 14 histologically verified brain areas with adequate sample size for statistical evaluation of MUA response. At high doses, all brain areas were affected. Included among the brain areas which were least affected by low doses were the caudate nucleus, septum, fornix, and medial forebrain bundle. Those areas that met the criteria for target sites of responding quickly (<5 min) to low doses (300 mg/kg) were: cerebellar cortex, cerebral cortex, hippocampus, lateral and medial geniculate nuclei, midbrain reticular formation, and pyriform cortex. In conjunction with the preliminary study [Brain Res. 70, 361 (1974)], the data indicate that the most ethanolsensitive tissue is found in the various kinds of cortex, cerebellar and cerebral (both paleocortex and neocortex).

Electroencephalographic-behavioral dissociations during animal hypnosis

Abstract 1. 1. Seventeen New Zealand White rabbits, with referential or bipolar electrodes in the motor cortex and various subcortical brain areas, were studied before and during hypnosis in 76 test sessions. 2. 2. Hypnosis was typically characterized by a reversible tonic immobility, relative unresponsiveness, decrease in muscle tone, and “arousal” EEG patterns. This state, although superficially similar to paradoxical sleep, was not the same, inasmuch as muscle tone was still present and there were no rapid eye movements, eyelid twitches, or phasic limb movements. 3. 3. After hypnosis was sustained for several minutes, a more “relaxed” state commonly occurred, wherein heart and respiratory rates decreased, muscle tone decreased further, and the EEG was of high voltage, slow activity. 4. 4. On 8 occasions in six rabbits, brief episodes of electrographic seizures occurred during hypnosis, without interrupting the tonic immobility. Seizures were induced in all rabbits with amphetamine, pentylenetetrazol, and the local anesthetic, dyclonine. Whether the drugs were injected before or during hypnosis, the motor component of the seizures was abolished by hypnosis, yet epileptiform EEG activity persisted during the apparent behavioral “sedation”. 5. 5. The “arousal” EEG, and especially the electrographic seizures, represented a conspicuous example of EEG-behavioral dissociation. Other similar dissociations have been reported in recent years, the best known of which are seen with paradoxical sleep, high doses of reserpine, certain neurological disorders, and physostigmine injection into chlorpromazine-sedated animals. 6. 6. The functional disconnection of motor activity in these states have common mechanisms. The existence of these several dissociation states emphasizes the limitations of current knowledge and the need for better understanding of sensori-motor interrelations.

Effects of electric stimulation of brain stem reticular formation on hippocampal theta rhythm and muscle activity in unanesthetized, cervical- and midbrain-transected rats

Abstract This study tested certain theories on the significance of hippocampal theta rhythm, as it relates to the descending motor functions of various levels of the brain stem reticular formation (BSRF). Electric stimulation of 100 sites of 10 unanesthetized, cervical-transected rats revealed that stimulation of either midbrain, pontine, or medullary BSRF simultaneously evoked hippocampal theta rhythm and increased EMG activity in vibrissae and neck muscles. Stimulation of 12 sites in 5 rats caused a brief ‘rebound’ EEG activation during which theta frequency increased over that during the stimulation; stimulation of 10 sites in 4 rats caused a rebound increase in EMG activity. Comparison of pulse duration effects (300/sec stimulation) showed that optimal activating responses occurred with 0.3 msec pulses, with no effect at durations longer than 1 msec. Comparison of frequency effects (0.3 msec pulses) showed that simultaneous EEG and EMG activations occurred at all frequencies tested between 100 and 300/sec. With higher frequency stimulation of 7 BSRF sites in 5 rats, hippocampal theta rhythm increased 1–4 waves/sec, and at 9 other sites in 5 rats, EMG response intensity increased progressively with slower stimulation frequencies. When the rats were paralyzed with curare, and their EMG activations blocked, EEG activations could still be elicited. In a given rat, curare decreased the frequency of stimulus-evoked theta by 0.5–2 waves/sec. Increasing stimulus voltage at 6 of the 16 BSRF sites tested in curarized rats increased theta frequency by 0.5–1.5 waves/sec, or converted it into low voltage, fast activity. Stimulation of 79 BSRF sites in 7 midbrain-transected rats consistently activated neck muscles, as well as one or more contralateral or ipsilateral forelimb muscles. Twenty-six patterns of forelimb muscle activation were observed, involving different degrees of contraction intensity in either or both flexor or extensor muscles on the same limb. Increasing the stimulus voltage in a given BSRF area increased the number of muscles responding and the intensity of their response.

Behavioral arrest: in search of the neural control system.

Scientists have spent hundreds of years trying to understand how the brain controls movement. Why has there been so little interest in knowing how the brain STOPS movement? This review calls attention to behavioral phenomena in which an animal or human undergoes temporary total-body arrest of movement, that is, behavioral arrest (BA). These states can be actively induced by visual stimuli, by body and limb manipulations, and by drugs. Historically, these states have been considered as unrelated, and their literature does not cross-connect. What is known about the causal mechanisms is scant, limited mostly to implication of the brainstem in manipulation-induced BA and dopaminergic blockade in the striatum in the case of drug-induced BA. The possibility has not been experimentally tested that all of these states share with each other not only an active global immobility in which awkward postures are maintained, but also underlying neural mechanisms. This review identifies key brainstem, diencephalic, and basal forebrain areas that seem to be involved in causing BA. We review the evidence that suggest a possible role in BA for the following brain structures: entopeduncular nucleus, medullary and pontine reticular zones, parabrachial region, pedunculopontine nucleus and nearby areas, substantia nigra, subthalamic nucleus, ventromedial thalamic nucleus, and zona incerta. Such areas may operate as a BA control system. Confirmation of which brain areas operate collectively in BA would require testing of several kinds of BA in the same animals with the same kinds of experimental tests. Areas and mechanisms might be elucidated through a strategic combination of the following research approaches: imaging (fMRI, c-fos), lesions (of areas, of afferent and efferent pathways), chemical microstimulation, and electrical recording (of multiple units and field potentials, with an emphasis on testing coherence among areas). We suggest the working hypothesis that BA is created and sustained by coherent, perhaps oscillatory, activity among a group of basal forebrain and brainstem areas that collectively disrupt the normal spinal and supraspinal sequencing controls of reciprocal actions on the extensors and flexors that otherwise produce movement.

Biological Water and Its Role in the Effects of Alcohol1

Alcohol and water compete with each other on target membrane molecules, specifically, lipids and proteins near the membrane surface. The basis for this competition is the hydrogen bonding capability of both compounds. But alcohols amphiphilic properties give it the capability to be attracted simultaneously to both hydrophobic and hydrophilic targets. Thus, alcohol could bind certain targets preferentially and displace water, leading to conformational consequences. This article reviews the clustering and organized character of biological water, which modulates the conformation of membrane surface molecules, particularly receptor protein. Any alcohol-induced displacement of biological water on or inside of membrane proteins creates the opportunity for allosteric change in membrane receptors. This interaction may also prevail in organelles, such as the Golgi apparatus, which have relatively low concentrations of bulk water. Target molecules of particular interest in neuronal membrane are zwitteronic phospholipids, gangliosides, and membrane proteins, including glycoproteins. FTIR and NMR spectroscopic evidence from model membrane systems shows that alcohol has a nonstereospecific binding capability for membrane surface molecules and that such binding occurs at sites that are otherwise occupied by hydrogen-bonded water. The significance of these effects seems to lie in the need to learn more about biological water as an active participant in biochemical actions. Proposed herein is a new working hypothesis that the molecular targets of ethanol action most deserving of study are those where water is trapped and there is little bulk water. Proteins (enzymes and receptors) certainly differ in this regard, as do organelles.

Dopaminergic mediation of reward: Evidence gained using a natural reinforcer in a behavioral contrast paradigm

Previous studies suggest a dopaminergic basis for the apparent reward properties of self-stimulation of certain brain areas with electrical current. The data of this present study indicate that there may be a dopaminergic role in the perceived hedonic quality of natural reinforcers. Using a classical behavioral contrast paradigm, we observed in rats that the perceived reward of a saccharin solution was decreased by haloperidol and increased by apomorphine, in doses that did not cause non-specific performance effects.

Alcohol, in a single pharmacological dose, decreases brain gangliosides

Alcohol penetrates into cell membranes, fluidizing and disordering the microenvironment. Here we report that associated with the disordering is a reduction of the normal level of brain gangliosides of adult male rats. The maximum decrement occurred in all major classes of gangliosides at 4 to 8 hours after a single pharmacological dose (3 gm/kg, IP). Because gangliosides have diverse, important functions in cell membranes, this effect of alcohol might be a basis for some of its intoxicating and addicting properties.