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C H Vanderwolf

Publications and source records attributed to C H Vanderwolf.

At least 73 records · Page 4Linked to original sources

Learning and behavioral-long-term potentiation: importance of controlling for motor activity.

A series of brief, high-frequency trains of electrical stimulation delivered to the perforant-path results in long-term potentiation (LTP) of the dentate gyrus as measured by average evoked potentials (EPs). Similar increases in dentate evoked potentials have been reported after natural learning. Previous studies of this behavioral LTP have not adequately controlled for ongoing behavior at the time of recording, even though motor activity also influences the amplitude of EPs. Chronically implanted rats were trained in both a radial-arm maze and an avoidance task using a crossover design. EPs in the dentate gyrus following perforant-path stimulation were recorded daily under 3 different behavioral conditions: immobility, movement, and freely behaving. After completion of both tasks, animals were given tetanizing stimulation of the perforant path. Results indicated strong improvements in the performance of both tasks. Tetanization induced significant LTP, which was still present at the end of 5 d. Significant differences were found between EPs collected during immobility and movement throughout the experiment. No evidence of behavioral LTP was observed, and the EPs remained consistent with baseline measures. These data show the necessity of controlling for ongoing behavior at the time of recording in electrophysiological studies of learning. The data also indicate that the phenomenon of behavioral LTP, as assessed by hippocampal EPs, is not universal to all learning experiences.

Animals↗

The role of serotonin in the control of cerebral activity: studies with intracerebral 5,7-dihydroxytryptamine.

Intact rats treated with centrally acting antimuscarinic (atropinic) drugs display large amplitude irregular slow waves in both the neocortex and hippocampus during behavioral immobility and some stereotyped automatic behaviors (Type 2 behavior). However, rhythmical slow activity in the hippocampus and low voltage fast activity in the neocortex occur in close correlation with spontaneous changes in posture, head movement, walking, rearing, swimming or struggling when held (Type 1 behavior). It has previously been proposed that these waveforms, jointly referred to as atropine-resistant cerebral activation (ARCA) are dependent on ascending serotonergic projections. As a further test of this hypothesis, we have studied rats in which forebrain levels of serotonin and 5-hydroxyindoleacetic acid were reduced to 3-10% of control levels as a result of multiple intrabrainstem injections of 5,7-dihydroxytryptamine. This treatment strongly reduced or abolished ARCA in most cases but did not reduce atropine-sensitive cerebral activation which appears to be dependent on ascending cholinergic projections from the basal forebrain to the cerebral cortex. Therefore, ARCA appears to be dependent on ascending serotonergic inputs to the forebrain.

5,7-Dihydroxytryptamine↗

A general role for serotonin in the control of behavior: studies with intracerebral 5,7-dihydroxytryptamine.

Multiple injections of 5,7-dihydroxytryptamine (5,7-DHT) into the rat brainstem reduced forebrain levels of serotonin and 5-hydroxyindoleacetic acid to 3-10% of the levels observed in control rats that had received intrabrainstem injection of a Locke's solution vehicle. This treatment reduced or abolished atropine-resistant cerebral activation (ARCA) in most cases. In rats in which ARCA was impaired or lost, a number of behavioral abnormalities were observed. These included: high levels of locomotion in an open field test; a deficiency in swimming to, and climbing upon, a visible platform in a water-filled tank; deficient social behavior; and impaired performance in a simple test of active avoidance. These deficits were not due to low level motor impairment. The 5,7-DHT-treated rats displayed a circadian rhythm of activity in running wheels. It is proposed that ascending serotonergic projections are an important component in the cerebral control of the Type 1 behavior with which the occurrence of ARCA is closely linked. Since Type 1 behavior includes such motor patterns as walking and manipulation of objects with the limbs, which are essential components of a great variety of behavioral performances, it is to be expected that a loss of ascending serotonergic function will result in a generalized deficit in behavior.

5,7-Dihydroxytryptamine↗

Neocortical and hippocampal electrical activity following decapitation in the rat.

It has been debated whether or not decapitation of conscious animals is a humane procedure. This problem may be clarified on the basis of recent research that has indicated that neocortical low voltage fast activity (LVFA) and hippocampal rhythmical slow activity (RSA) can result from activity in either the cholinergic corticipetal projections from the basal forebrain or the serotonergic corticipetal projections from the brainstem. These inputs appear to produce, respectively, atropine-sensitive LVFA and RSA and atropine-resistant LVFA and RSA. In waking animals, atropine-resistant LVFA and RSA occur only in close correlation with motor activities such as spontaneous changes in posture, walking or struggling (Type 1 behavior). Painful stimuli readily elicit both Type 1 behavior and LVFA and RSA in atropine-treated rats. Atropine-sensitive LVFA and RSA may occur in anesthetized as well as in conscious animals, but atropine-resistant LVFA and RSA are generally absent during anesthesia. In the experiments reported here, rats were decapitated: (1) in the normal waking state; (2) after pretreatment with atropine or scopolamine; or (3) following induction of anesthesia with ethyl ether. Clear hippocampal RSA and neocortical LVFA were observed in conditions 1 and 3 but not in condition 2. It is concluded: (A) that atropine-sensitive LVFA and RSA are not good indices of conscious perception of pain since these waveforms occur during anesthesia as well as in the waking state; and (B) that the cerebral reaction to decapitation does not resemble the usual cerebral reaction to painful stimuli. This is consistent with the view that decapitation is not inhumane.

Animals↗

Are emotion and motivation localized in the limbic system and nucleus accumbens?

Groups of control rats without surgery or groups of rats prepared with surgical lesions of the septal nuclei, amygdala, cingulate cortex, accumbens nucleus, section of the fornix, or sham surgical operations, were tested in a simple autonomic conditioning situation (conditioned defecation). Control rats and rats with lesions of the accumbens nucleus were also tested in a straight alley maze under varying conditions of water deprivation. In general, the lesions had little effect except that amygdaloid damage impaired acquisition of conditioned defecation. The theory that 'emotion' and 'motivation' can be localized in the 'limbic system' and nucleus accumbens is discussed critically.

Animals↗

Thalamic control of neocortical activation: a critical re-evaluation.

Bilateral intrathalamic injection of kainic acid in rats produces widespread destruction of thalamic neurons but does not abolish neocortical activation (generation of low voltage fast activity, LVFA). On the other hand, a combination of reserpine and scopolamine abolishes all LVFA but does not abolish thalamocortical transmission as assessed by recruiting responses, augmenting responses, and sensory evoked neocortical potentials. These facts show that thalamocortical transmission is neither necessary nor sufficient to produce neocortical activation. The classical view of neocortical activation as dependent on a reticulothalamocortical pathway seems to be incorrect. It appears, instead, that neocortical activation is dependent jointly on a cholinergic input from the basal forebrain and a serotonergic input from the brainstem.

Animals↗

Activity of identified cortically projecting and other basal forebrain neurones during large slow waves and cortical activation in anaesthetized rats.

To examine the role played by the basal forebrain cholinergic system in cortical activation, neuronal activity was investigated in the globus pallidus and substantia innominata of urethane-anaesthetized rats during large cortical slow waves and spontaneous or elicited low voltage fast activity. An effort was made to identify the neurones by antidromic stimulation from the neocortex (supposedly cholinergic cells) and from the subthalamic nucleus (pallidal cells). Most of the cortically projecting neurones were strongly activated during cortical activation (5-fold increase in firing rate on average), while the discharge rate of pallidal units was increased only slightly (ratio 1.25 on average). In contrast to the cortically projecting cells, some unidentified cells in the substantia innominata fired at a much higher rate during large cortical slow waves as compared to low voltage fast activity. The results are discussed in relation to previous work on the cortically projecting cells and on the mechanisms of cortical activation.

Anesthesia, General↗

Hippocampal rhythmical slow activity following ibotenic acid lesions of the septal region. I. Relations to behavior and effects of atropine and urethane.

The effects of intraseptal injections of various concentrations of ibotenic acid on hippocampal electrical activity were studied in freely moving and urethane-anesthetized rats. Ibotenic acid selectively abolished the atropine-sensitive form of hippocampal rhythmical slow activity (RSA) normally seen during urethane anesthesia. Large amplitude irregular activity (LIA) and RSA in the waking state were somewhat depressed as well. Despite this, clear RSA persisted in the waking state in association with locomotion or struggling (Type 1 behavior). As in normal rats, such RSA was resistant to systemic administration of atropine. Analysis of brain sections stained with gallocyanin or for acetylcholinesterase showed that ibotenic acid produced cell loss in the dorsal lateral septal nucleus and the septohippocampal nucleus. Cells in the medial septal and diagonal band nuclei were resistant to ibotenic acid. The results suggest that intrinsic septal circuitry is critically involved in the generation of the atropine-sensitive (presumably cholinergic) form of RSA. The mechanisms by which LIA and the two forms of RSA are generated in the hippocampus is discussed.

Animals↗

Hippocampal rhythmical slow activity following ibotenic acid lesions of the septal region. II. Changes in hippocampal activity during sleep.

Ibotenic acid injections in the septal nuclei of the forebrain produced severe cell loss in the dorsal lateral septal nucleus and the septohippocampal nucleus. Chronic recording of hippocampal and neocortical slow-wave activity and muscle activity showed that the ibotenic acid treatment had selectively abolished the atropine-sensitive (presumably cholinergic) form of hippocampal rhythmical slow activity (RSA) normally seen during the tonic component of active sleep. Large-amplitude irregular activity (LIA), that is normally associated with waking immobility and quiet sleep, and the atropine-resistant (probably serotonergic) RSA that normally accompanies phasic muscular activity during active sleep, were also somewhat depressed. However, clear RSA was seen during phasic muscular activity in active sleep and LIA was clearly seen during quiet sleep in all rats. Neocortical activity was not affected by the ibotenic acid treatment. The results are consistent with the hypothesis that, both in the sleeping and the waking state, RSA can be produced by either of two distinctive inputs to the hippocampus. No support was found for the hypothesis that RSA during active sleep has a different basis than RSA in the waking state.

Animals↗

Suppression of serotonin-dependent cerebral activation: a possible mechanism of action of some psychotomimetic drugs.

Rats treated with centrally acting anti-muscarinic (atropinic) drugs display large amplitude irregular slow waves in both the neocortex and hippocampus during behavioral immobility and some stereotyped automatic behaviors (Type 2 behavior). However, rhythmical slow activity (RSA) in the hippocampus and low voltage fast activity (LVFA) in the neocortex occur in close correlation with spontaneous changes in posture, head movement, walking, rearing, swimming or struggling when held (Type 1 behavior). Previous research has indicated that such atropine-resistant RSA and LVFA is dependent on brain serotonin. In the experiments reported here, atropinized rats were given a test drug or a control injection while hippocampal and neocortical activity and behavior were recorded. Several psychotomimetic drugs (phencyclidine; (d,l)-N-allyl-N-normetazocine (SKF-10,047); d,l-cyclazocine; and N-ethyl-1-phenyl-cyclohexylamine) strongly suppressed atropine-resistant RSA and LVFA in doses that were compatible with active behavior. Ketamine had a weak effect but a variety of other drugs were inactive in this test. It is suggested that the psychotomimetic effect of phencyclidine and the psychotomimetic opioids is due, at least in part, to suppression of serotonin-dependent activation of the cerebral cortex.

Animals↗

Electrophysiological correlates of stereotyped sniffing in rats injected with apomorphine.

Macroelectrodes were chronically implanted in the olfactory bulb, dorsal hippocampus, neocortex and under the mystacial pad in a group of rats. Recordings were taken during spontaneous behavior, during exploration of novel objects and odorous material, and during handling. Similar observations were made following injection of apomorphine (1.25-5 mg/kg, SC). The lower dose of apomorphine elicited a pattern of sniffing, olfactory bulb activity and vibrissal EMG which resembled closely the patterns observed in undrugged rats sniffing while in tactile contact with a novel object. However, unlike normal rats, the apomorphine-treated rats did not orient toward novel objects or odors. Apomorphine also elicited nearly continuous hippocampal rhythmical slow activity which occurred in correlation with head movements and locomotion. It is suggested that apomorphine elicits a motor pattern which resembles normal contact sniffing but which, unlike normal sniffing, is relatively impervious to control by visual and olfactory stimuli.

Animals↗

Hippocampal electrical activity in relation to behavior following ethylcholine aziridinium ion (AF64A) treatment.

The effects of intracerebroventricular (ICV) injections of ethylcholine aziridinium ion (AF64A; 3 nmol/3 microliters/side) on the pattern of hippocampal electrical activity were studied in freely moving and urethane anesthetized rats. AF64A treated rats showed a significantly smaller increase in 6-12 Hz hippocampal rhythmical slow activity (RSA) with struggling in the no drug condition in comparison to the vehicle injected rats. However, neither AF64A treatment nor a control injection abolished the presumed cholinergic form of RSA that is present during urethane anesthesia. Systemic injection of atropine in waking rats did not significantly alter RSA in either the AF64A or vehicle injected rats. Analysis of histological brain sections revealed extensive damage to the fimbria-fornix, CA3 of the hippocampus, corpus callosum, neocortex and striatum. Acetylcholinesterase staining of the remaining hippocampus appeared normal in the AF64a treated rats. The data indicate that the depletion of cholinergic markers in the hippocampus following ICV administration of AF64A is not sufficient to disrupt the cholinergic form of RSA. Further, the question is discussed as to whether AF64A produces its cholinoselective effects via a specific pharmacological action or through a nonspecific destruction of the fimbria-fornix.

Animals↗

Transcallosal evoked potentials in relation to behavior in the rat: effects of atropine, p-chlorophenylalanine, reserpine, scopolamine and trifluoperazine.

Single pulse electrical stimulation of the sensorimotor cortex in waking rats produced an evoked response in the contralateral sensorimotor cortex. The slow wave response consisted of: (1) an early component that was negative at the pial surface and in layer V, and was associated with multiunit discharge; and (2) a late component that was mainly negative at the surface, positive in layer V, and was associated with multiunit suppression. Previous research suggests that the early component represents summed excitatory postsynaptic potentials; the late component summed inhibitory postsynaptic potentials. Both components could be elicited by direct stimulation of the corpus callosum and both were abolished by midline callosal section. The amplitude and duration of the late component varied with concurrent motor activity in a striking manner. It was large during waking immobility and also during face-washing, licking the paws, chewing food and drinking water, but was much reduced or absent during head movements, walking and changes in posture. Only minor changes were associated with the transition from waking immobility to slow wave sleep. A series of pharmacological experiments indicated that the behavior-related variation in the late component of the transcallosal evoked response was dependent on both cholinergic and serotonergic transmission.

Animals↗

Near-total loss of 'learning' and 'memory' as a result of combined cholinergic and serotonergic blockade in the rat.

Previous work has indicated that activation of the cerebral cortex (i.e. elicitation of low-voltage fast activity in the neocortex and rhythmical slow activity in the hippocampus) is dependent on corticipetal cholinergic and serotonergic projections. Treatment with a combination of p-chlorophenylalanine (an inhibitor of the synthesis of serotonin) plus atropine or scopolamine (muscarinic cholinergic antagonists) can suppress all cerebral activation. In this paper, the behavioral effects of single or combined blockade of cholinergic and serotonergic neurotransmission were studied using a shock avoidance test, an open field test, a swim-to-platform test, a hypothalamic self-stimulation test and a test of grooming behavior. The results show that blockade of cerebral activation produces a condition analogous to global dementia but does not produce sleep or coma. The hypothesis that cholinergic and serotonergic neurotransmission provides a basis for learning and memory is discussed critically.

Animals↗

Evidence that serotonin mediates non-cholinergic neocortical low voltage fast activity, non-cholinergic hippocampal rhythmical slow activity and contributes to intelligent behavior.

Previous research has shown that low voltage fast activity (LVFA) in the neocortex and rhythmical slow activity (RSA) in the hippocampus can result from activity in either of two ascending pathways. Activity in neurons in the basal forebrain may produce atropine-sensitive (presumably cholinergic) LVFA and RSA during both Type 1 behavior (e.g., head movement, walking) and Type 2 behavior (e.g., waking immobility, face-washing, tremor). Activity in an aminergic pathway may produce atropine-resistant LVFA and RSA during Type 1 behavior only. The role of 5-hydroxytryptamine (5-HT) in this pathway was studied in rats treated with p-chlorophenylalanine (PCPA; 500 mg/kg/day X 3, i.p.). Amine levels were measured by high pressure liquid chromatography with electrochemical detection. Brain slow wave and multi-unit activity was assessed by inspection and by a procedure of filtering and integration. PCPA treatment alone had little effect on LVFA or RSA, but following PCPA and atropine (50 mg/kg) together, both LVFA and RSA were attenuated or eliminated. Thus, atropine-resistant LVFA and RSA may be dependent on 5-HT transmission. A combination of PCPA and atropine produced a very severe deficit in performance in a simple water maze. Rats treated with this drug combination may provide an animal model of human global dementia.

Animals↗

Joint cholinergic-serotonergic control of neocortical and hippocampal electrical activity in relation to behavior: effects of scopolamine, ditran, trifluoperazine and amphetamine.

Previous research has indicated that low voltage fast activity (LVFA) in the neocortex and rhythmical slow activity (RSA) in the hippocampus can result from activity in either (or both) the cholinergic corticipetal projections from the basal forebrain and the serotonergic corticipetal projections from the brainstem raphe. These inputs appear to give rise, respectively, to atropine-sensitive LVFA and RSA and atropine-resistant LVFA and RSA. The atropine-sensitive and atropine-resistant waveforms have been shown to have distinctive behavioral correlates. The present experiments extend these findings by providing dose-response data on the effects of scopolamine and Ditran on neocortical activity in relation to behavior in the rat. In addition, new evidence is presented which indicates that neuroleptic drugs reduce activity in the atropine-resistant (presumably serotonergic) inputs to the hippocampus and neocortex by an indirect action involving dopamine receptors. A single dose of d-amphetamine or apomorphine appears to increase activity in the same pathway by a similar indirect action. These findings may be relevant to the psychiatric effects of neuroleptic drugs.

Acetylcholine↗

Pathways through cingulate, neo- and entorhinal cortices mediate atropine-resistant hippocampal rhythmical slow activity.

Rats prepared with a lesion separating the entorhinal cortex from the neocortex and cingulate cortex displayed apparently normal hippocampal rhythmical slow activity (RSA) with a frequency of 6-12 Hz in both CA1 and dentate gyrus during Type 1 behavior (locomotion, head movements, changes in posture). Variations in the commissural average evoked potential (AEP) and increased power in the 30-100 Hz range (fast waves) also correlated with Type 1 behavior. Urethane did not abolish the RSA. However, systemic administration of atropinic drugs eliminated all RSA and eliminated or attenuated the Type 1 behavior-related variations in the AEP and fast waves. Thus, the normally present atropine-resistant RSA was eliminated by the cortical lesion while atropine-sensitive RSA remained intact. Removal of cingulate cortex alone was partially effective in suppressing atropine-resistant RSA but a lesion of the neocortex only, sparing cingulate cortex, had a minimal effect on it. Lesions of the amygdala, the anterior or medial thalamus or the cerebellum had little or no effect on atropine-resistant RSA. Previous work has shown that lesions of the entorhinal cortex or lateral hypothalamus eliminate atropine-resistant RSA. We suggest that atropine-resistant RSA is mediated by a somewhat diffuse pathway which traverses the hypothalamus, cingulate cortex, and neocortex before reaching the hippocampus via the entorhinal cortex.

Animals↗