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C H Vanderwolf

Publications and source records attributed to C H Vanderwolf.

At least 19 recordsLinked to original sources

Scopolamine blocks olfaction-induced fast waves but not olfactory evoked potentials in the dentate gyrus.

The presentation of some odorous materials such as xylene or toluene under the snout of rats has been shown to elicit 15-30 Hz fast-wave bursts in both the olfactory bulb and dentate gyrus. Electrical stimulation of the olfactory bulb elicits an evoked potential (latency of first peak is 16-18 ms) in the dentate gyrus. The present study demonstrates that scopolamine or atropine blocks toluene-induced fast-wave bursts in the dentate region and to a lesser degree in the olfactory bulb while leaving dentate gyrus electrically evoked potentials intact. Further, rhythmical burst stimulation of the olfactory bulb at fast-wave frequencies will elicit fast-wave-like oscillations in the dentate gyrus. These fast-wave-like events, unlike evoked potentials to single-pulse stimulation, are abolished after muscarinic receptor antagonism with atropine. Mechanisms at the olfactory bulb and dentate gyrus that produce fast oscillations may involve muscarinic cholinergic synapses while the simple transmission of single, non-oscillatory olfactory signals to the dentate gyrus does not.

Animals

p-chlorophenylalanine-induced serotonin depletion: reduction in exploratory locomotion but no obvious sensory-motor deficits.

Para-chlorophenylalanine (PCPA) depletes central serotonin (5-hydroxytryptamine, 5-HT) by inhibiting tryptophan hydroxylase, an enzyme necessary for the synthesis of 5-HT. The effects of a wide range of PCPA doses (150-1000 mg/kg) on spontaneous exploratory locomotor activity in a novel environment, activity in running wheels and a number of sensory-motor capacities were examined. Administration of 1000 mg/kg PCPA reduced whole brain levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid to 9.4 and 8.2% of control levels, respectively. Treatment with PCPA produced a dose-dependent decrease in exploratory locomotion in an unfamiliar automated open field relative to vehicle-treated animals. Further, all measures of general, horizontal and vertical activity were suppressed by PCPA treatment. In contrast to previous work, hyperactivity of rats chronically housed in cages with running wheel access was not observed. In their home cages, some PCPA-treated rats exhibited hyper-reactivity to cutaneous stimulation. No other sensory-motor deficits were apparent. Previous theories of 5-HT function state that its action may be to inhibit motor activity or promote sleep. The present results challenge this view and suggest that 5-HT, at least in certain environments, may stimulate locomotor activity without directly controlling various sensory-motor capacities in rats.

Animals

Some general anesthetics reduce serotonergic neocortical activation and enhance the action of serotonergic antagonists.

In urethane-anesthetized rats, neocortical LVFA induced by 100 Hz electrical stimulation of the median raphe area or by tail pinching was completely eliminated by a combination of scopolamine (5 mg/kg, IP) and p-chlorophenylalanine (500 mg/kg/day x 3, IP), providing evidence that LVFA is dependent on cholinergic-muscarinic and serotonergic inputs to the neocortex in urethane-anesthetized as well as in freely moving rats. The serotonergic receptor antagonists ketanserin and methiothepin (1-10 mg/kg, IP) also produced a dose-dependent blockade of LVFA in urethane-anesthetized rats, and eliminated virtually all LVFA when combined with scopolamine. A combination of diethyl ether anesthesia and scopolamine completely eliminated all neocortical LVFA without additional antiserotonergic treatment, and a combination of chloral hydrate anesthesia and scopolamine similarly blocked all LVFA in about 50% of the rats tested. In the remaining chloral hydrate-anesthetized rats, the residual LVFA could be eliminated by the serotonergic antagonist ritanserin (10 mg/kg, IP). As shown previously, in nonanesthetized rats treated with scopolamine, LVFA can be maintained by a serotonergic input to the neocortex. The present data suggest that some general anesthetics reduce or completely abolish this serotonergic LVFA. Further, the serotonergic antagonists used here exert much stronger antiserotonergic effects in rats anesthetized with urethane or chloral hydrate than in freely moving rats. Therefore, studies of serotonergic transmission or antagonist action, especially in the neocortex, in anesthetized rats may not be applicable to the waking state.

Anesthetics, General

The behavioral neurobiology of learning and memory: a conceptual reorientation.

Research on the neurobiology of learning and memory has been guided by two major theories: (i) memory as a psychological process and (ii) memory as a change in synaptic neural connectivity. It is not widely recognised that not only are these theories different but, moreover, they are fundamentally incompatible. Confusion concerning basic concepts in the learning and memory field in mammals has lead to the creation of an extensive but often inconclusive experimental literature. However, one important conclusion suggested by recent work in this field is that experience-dependent changes in neural connectivity occur in many different brain systems. Particular brain structures, such as the hippocampus, do not play any uniquely important role in experience-dependent behavior. Research in learning and memory can be best pursued on the basis of biological studies of animal behavior and a cellular approach to brain function.

Animals

Behavior-related cortical activity and swim-to-platform performance in the aged rat.

Aged rats (26 months) usually retained normal acetylcholine-dependent and serotonin-dependent forms of neocortical low-voltage fast activity and serotonin-dependent hippocampal rhythmical slow-wave activity. In a simple swim-to-platform test, aged rats (23 and 26 months) performed normally in acquisition and in retention over a 7-day period. The results are discussed in relation to the common assumption that aged rats provide a valid model of human senile dementia.

Acetylcholine

Serotonin-dependent cerebral activation: effects of methiothepin and other serotonergic antagonists.

In scopolamine-treated (5.0 mg/kg, s.c.) rats hippocampal rhythmical slow activity (RSA) and neocortical low voltage fast activity (LVFA) occur only in close correlation with head movements, spontaneous changes in posture, or locomotion (Type I behavior). Previous work indicates that such scopolamine-resistant RSA and LVFA are dependent on ascending serotonergic projections. A test of 9 serotonergic antagonists (methiothepin; ritanserin; ketanserin; pizotifen; mianserin; pirenperone; ICS-205-930; metoclopramide; methysergide) showed that methiothepin produces a partial reduction in RSA and LVFA in scopolamine-treated rats, while the other antagonists are completely inactive over a wide range of doses. It may be that serotonergic cerebral activation depends on both 5-HT1 and 5-HT2 receptors.

Animals

Hippocampal activity, olfaction, and sniffing: an olfactory input to the dentate gyrus.

Experiments in freely moving rats showed that olfactory stimuli elicit a burst of rhythmical 15-30 Hz waves in or near the hilus of the dentate gyrus but not in adjacent regions of CA1. This fast wave burst is not elicited by visual, auditory, or somatosensory inputs and is not related to motor activity. Electrical stimulation of the olfactory bulb evokes a complex potential in the hilus of the dentate gyrus but not in adjacent regions of CA1. Experiments making use of wave-triggered averaging demonstrated that there is a degree of phase-locking between (a) hippocampal RSA and sniffing or other respiratory patterns, (b) hippocampal RSA and the initiation of jumping, and (c) respiration and the initiation of jumping. An early hypothesis that the hippocampus and dentate gyrus are part of an olfacto-motor mechanism may merit re-examination.

Animals

Hippocampal electrical activity in the female rat: the estrous cycle, copulation, parturition, and pup retrieval.

Hippocampal electrical activity was examined in female rats across the four phases of the estrous cycle, as well as during copulation, parturition, and pup retrieval. Possible hormonal effects on hippocampal activity were examined by recording daily during struggling and immobility throughout five estrous cycles. No differences in the characteristics of rhythmical slow activity (RSA), large-amplitude irregular activity (LIA), or their relation to behavior were found between the phases of the estrous cycle. Behaviors examined during copulation were lordosis, hopping, and ear wiggling. Lordosis and ear wiggling were both accompanied by irregular waves, with some low frequency RSA also present during lordosis. Hopping was accompanied by RSA which was greater in amplitude and frequency than RSA during walking. Parturition behaviors examined included body extensions, genital or pup licking, and 'body flattening'. Body extensions were found to be associated with irregular hippocampal activity, and appeared to be a Type 2 behavior. Interestingly, sudden suppressions of the hippocampal record lasting 1-5 s often preceded body extensions. Irregular hippocampal activity was present at all times during genital and pup licking. Body flattening was typically accompanied by very high amplitude irregular waves which, although the rats were awake, resembled a sleeping hippocampal pattern. Pup retrieval involved walking and was thus always accompanied by RSA.

Animals

Pressure on the snout immobilizes the spontaneously active, scopolaminized, and amphetaminized hyperactive rat.

Rats that are brought into a novel environment or that are given stimulants or anti-muscarinic drugs exhibit high levels of motor activity. Application of moderate pressure on the sides of the snout of such rats results in immediate cessation of all movements for extended time periods. Hippocampal electrocorticograms show that hippocampal slow wave activity during such induced immobility is equivalent to the hippocampal slow wave pattern typically associated with spontaneous immobility. However, neocortical activity following scopolamine administration contains more 2-6 Hz irregular activity during spontaneous than induced immobility.

Animals

The electrocorticogram in relation to physiology and behavior: a new analysis.

Recent research in animals indicates that the generalized regulation of cortical activity that is represented by activation of the electrocorticogram is dependent on ascending cholinergic and serotonergic projections. The effect of the activity of these systems is correlated with concurrent motor activity in a detailed and specific manner. Combined blockade of central cholinergic and serotonergic function results in impaired cerebral control of behavior, i.e., a dementia-like syndrome. Previous concepts, which held that electrocortical activation is mediated via a reticulo-thalamo-cortical pathway and that it is related primarily to arousal, vigilance, and the sleep-waking cycle appear to be incomplete or erroneous.

Animals

Effects of raphe stimulation on hippocampal and neocortical activity and behaviour.

In chronically prepared rats, electrical stimulation (100 Hz, 0.1 ms pulses) of the dorsal raphe nucleus, some sites in the median raphe nucleus, and adjoining regions of the midbrain produced locomotion accompanied by hippocampal rhythmical slow activity (RSA) and neocortical low voltage fast activity (LVFA). Both the behaviour and the cerebral waveforms persisted after injection of scopolamine HBr (5 mg/kg, s.c.). Median raphe stimulation usually produced behavioural freezing or an unnatural forced movement accompanied by RSA and LVFA. The behavioural response and the LVFA were not affected by scopolamine but scopolamine eliminated the RSA, replacing it with a low amplitude irregular (suppressed) pattern. p-Chlorophenylalanine (PCPA, 500 mg/kg/day x 3, i.p.) reduced the RSA and LVFA normally present during walking after scopolamine but did not reduce the hippocampal suppression produced by median raphe stimulation in scopolamine-treated rats. Hippocampal suppression and LVFA in response to median raphe stimulation were also present in urethane (1.0-1.5 g/kg, i.p.) anesthetized rats, whether pretreated with PCPA or not. Stimulation at most other midbrain sites produced RSA and LVFA in the urethane condition. RSA was abolished in the urethane plus scopolamine condition. The data support the view that scopolamine-resistant RSA and LVFA are dependent on serotonergic projections. The hippocampal suppression produced by median raphe stimulation may be dependent on non-serotonergic neurotransmission.

Animals

Anti-muscarinic drug effects in a swim-to-platform test: dose-response relations.

Rats were given subcutaneous or intraperitoneal injections of scopolamine, intraperitoneal injections of atropine, or control injections, and trained on a simple swim-to-platform task. Errors were proportional to dose for both drugs over a wide range. No difference was found in the effects of intraperitoneal or subcutaneous scopolamine but scopolamine was 25 times more potent than atropine. The potency of both drugs in impairing swim-to-platform behavior was similar to their potency in abolishing the cholinergic component of neocortical low voltage fast activity. The electrocortical effect of anticholinergic drugs may be a major factor in the behavioral impairment they produce.

Animals

The effects of serotonergic stimulation on hippocampal and neocortical slow waves and behavior.

The effect of central serotonergic stimulation on hippocampal and neocortical electrical activity and behavior was studied in freely moving rats by administering: (a) tranylcypromine followed by tryptophan, (b) fluoxetine followed by 5-hydroxytryptophan, or (c) p-chloroamphetamine alone. In all rats, scopolamine-resistant hippocampal rhythmical slow activity (RSA), thought to be dependent on brain serotonin, maintained its normal relation to behavior, occurring in close correlation with Type 1 behaviors (postural changes, turning of the head, walking). This RSA was generally absent during stereotyped behavior (head weaving, forepaw treading, hindlimb splaying and tremor). Scopolamine-resistant neocortical low-voltage fast activity (LVFA), also though to be dependent on brain serotonin, was present during Type 1 behaviors and also during stereotyped behavior. Most rats that developed a full stereotyped behavior syndrome had behavioral and electrocortical seizures which were associated with a reduction in the amplitude of hippocampal activity. These seizures were suppressed by methysergide or benserazide. Metergoline (and methysergide to a lesser extent) suppressed the stereotypic behaviors of the serotonin syndrome, resulting in a striking increase in the locomotion caused by central serotonergic stimulation. Such locomotion was accompanied by RSA and LVFA. It was concluded that increased serotonergic activity in the CNS causes an increase in motor activity and a correlated increase in scopolamine-resistant hippocampal RSA and scopolamine-resistant neocortical LVFA and suggested that metergoline blocks serotonin receptors mediating stereotyped behaviors, thereby permitting the expression of serotonin-mediated locomotion.

5-Hydroxytryptophan

Animal models of human amnesia and dementia: hippocampal and amygdala ablation compared with serotonergic and cholinergic blockade in the rat.

The behavioral effects of combined bilateral hippocampal and amygdala ablation (previously proposed as a model of human global amnesia) were compared to those seen with central blockade of the ascending cholinergic and serotonergic projections (a possible model of human global dementia) in male hooded rats. Rats were prepared with: (a) bilateral surgical lesions of the hippocampus and amygdala; (b) pharmacological blockade of central cholinergic and serotonergic function by systemic injections of scopolamine and p-chlorophenylalanine; and (c) neurotoxic lesions of the rostrally projecting serotonergic nuclei in the brainstem using intracerebral injections of 5,7-dihydroxytryptamine, later combined with scopolamine. The behavioral tests used were: an open field test, a swim-to-platform test, and a Lashley III maze. In all 3 tests, rats with either the neurotoxin lesions plus scopolamine or p-chlorophenylalanine plus scopolamine treatment showed greater impairments in comparison with controls than did the combined lesion group. These results indicate that simultaneous blockade of central serotonergic and cholinergic transmission has a greater effect on some aspects of the organization of behavior than large surgical lesions of the hippocampus and amygdala.

Amnesia

Behavioural effects of neocortical and cingulate lesions in the Mongolian gerbil.

The experiments examine the effects of cortical lesions on a variety of behaviours in the Mongolian gerbil (Meriones unguiculatus). Gerbils with either large anterior or posterior lesions were compared with normal gerbils by administering a battery of tests of rodent behaviours such as grooming, eating, social interaction, ventral marking and foot-stomping. In a second experiment, a more detailed investigation was carried out of the effects of focal cortical lesions on ventral marking. The results of these experiments suggest that anterior cortical lesions in gerbils give rise to a number of different deficits in behaviour. The results further suggest that cingulate cortex is part of the neural substrate for ventral marking behaviour. The implications of these results for contemporary theories of frontal lobe function are discussed.

Animals

Intracortical grafts of embryonic basal forebrain tissue restore low voltage fast activity in rats with basal forebrain lesions.

Unilateral injections of kainic acid into the basal forebrain in a series of rats resulted in an increase in large amplitude slow waves, a correlated burst-suppression pattern of multi-unit activity, and a decrease in acetylcholinesterase staining in the neocortex ipsilateral to the kainic acid injection. Subsequently, a cell suspension, prepared from rat embryonic basal forebrain tissue, was injected adjacent to the recording electrodes ipsilateral to the kainic acid injection. This produced a gradual recovery of low voltage fast activity (LVFA) and a correlated continuous discharge pattern of multi-unit activity in the neocortex ipsilateral to the kainic acid injection. LVFA recovered more slowly at neocortical recording sites that received an injection of a cell suspension of hippocampal primordial cells or no injection at all. Acetylcholinesterase-positive fibers from the basal forebrain tissue invaded host cortex; no comparable outrgrowths were demonstrable in the hippocampal primordium tissue grafts. Restoration of cholinergic electrocortical activation may play an important role in the improvements in behavioral performance produced by basal forebrain grafts in the cortex in animals with basal forebrain lesions.

Acetylcholinesterase