Mapping of globus pallidus and ventral pallidum lesions that produce hyperkinetic treading

The purpose of this study was to identify sites where striatopallidal lesions produce two distinct sensory-triggered hyperkinetic syndromes: (1) exaggerated forelimb treading alone to oral taste infusions and (2) sensorimotor exaggerated treading plus enhanced aversive reactions to taste infusions. The behavioral characteristics of these syndromes have been described previously (Berridge, K.C. and Cromwell, H.C., Behav. Neurosci., 104 (1990) 778-795). Bilateral excitotoxin lesions were made using quinolinic acid (10 micrograms in 1 microliter) in the caudate/putamen, nucleus accumbens, globus pallidus or ventral pallidum/substantia innominata. In order to identify the precise center, borders, severity and size of lesion sites that caused these hyperkinetic treading syndromes, neuron counts (modified fractionator technique) and glial fibrillary acidic protein immunoreactivity (GFAP-IR) densitometry were used in a stereological mapping analysis. The site of lesions that produced the hyperkinetic treading syndrome without enhanced aversion was found to be restricted to the globus pallidus (GP). Damage exceeding 60% neuron loss bilaterally within a 0.8 x 1.0 x 1.0 mm subregion of the ventromedial GP produced this syndrome. The site of lesions that produced the combined syndrome of hyperkinetic treading and aversive enhancement was ventral to the globus pallidus, within the ventral pallidum/substantia innominata (VP/SI). Damage exceeding 70% neuron loss bilaterally within a 1.0 x 0.5 x 1.0 mm diameter subregion of the ventromedial ventral pallidum/substantia innominata produced this syndrome. This subterritory was located immediately lateral to the border of the lateral hypothalamus. Bilateral lesions to the caudate/putamen or nucleus accumbens did not produce either hyperkinetic treading syndrome. These results are discussed in terms of the connectivity of the ventral pallidal/substantia innominata and globus pallidus regions and in terms of neuropathological models of hyperkinetic disorders.     

Delayed-nonmatching-to-sample performance is impaired by extensive, but not by limited, lesions of the thalamus in the rat.

Two experiments were conducted to determine whether lesions affecting limited areas of the thalamus can impair the performance of rats on a spatial delayed-nonmatching-to-sample (DNMTS) task trained before surgery. In Exp 1, DNMTS was not affected by lesions produced by injecting 5 μl of 1 mM N-methyl-D-aspartate (NMDA) into either the midline thalamus (n?=?16) or bilaterally 1.0 mm from the midline (n?=?16). In Exp 2, radio-frequency lesions were made 1.0 mm lateral from the midline at 3 anterior–posterior locations that destroyed the full rostral–caudal extent of the lateral internal medullary lamina (L-IML; n?=?8), or at single anterior–posterior locations that destroyed either the anterior (n?=?8) or posterior (n?=?8) portions of the L-IML site. Although complete L-IML lesions disrupted DNMTS performance to an extent comparable to that of another study (R. G. Mair and D. M. Lacourse; see record 1992-42024-001), lesions that were restricted to either the anterior or posterior portion of the L-IML site had no significant effect on this task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recollection is impaired by the modification of interpretation bias.

The interpretation paradigm of cognitive-bias modification (CBM-I) was modified with instructions used in process-dissociation procedures for the purpose of investigating processes contributing to performance on the transfer task. In Experiment 1, nonanxious students were trained to interpret ambiguous situations in either a negative or benign way (or they read nonambiguous scenarios). They were then asked to respond to new ambiguous situations, in the same way as contextually similar analogues during training, or to respond differently. Benign training proactively impaired memory for negative outcomes. This effect was replicated by anxious students in Experiment 2 and discussed with respect to the assumptions underlying process-dissociation procedures and directions for future research. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Procedures that produce context-specific tolerance to morphine in rats also produce context-specific withdrawal.

Rats previously injected with morphine in the presence of a distinct environment (paired animals) were more tolerant to the analgesic effects of morphine in that environment than were rats previously injected with morphine in another environment (unpaired animals). When injected with saline instead of morphine in the distinct environment, paired animals were more reactive to pain (hyperalgesic) than unpaired animals, but no more reactive to pain than animals never given morphine. More important, the paired animals also exhibited more withdrawal symptoms (wet dog shakes, genital licking, circling, rearing, and defecation) during abstinence and naltrexone-precipitated withdrawal in the distinct environment than did the unpaired and saline animals. Thus, procedures that are capable of providing context-specific opiate tolerance are also capable pf producing context-specific opiate withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Haloperidol reinstates latent inhibition impaired by hippocampal lesions: Data and theory.

The effect of haloperidol administration on the impairment of latent inhibition produced by aspirative lesions of the hippocampus was examined in the rat eyeblink response preparation. During the preexposure phase, rats with hippocampal or control lesions were either exposed to a tone or allowed to sit in the training apparatus. During the conditioning phase, the tone was paired with an airpuff to the eye after the rats were injected with either saline or haloperidol. Although saline-injected rats with hippocampal lesions did not show latent inhibition, the phenomenon was reinstated in rats that received haloperidol injections. A possible locus of the interaction between hippocampal lesions and haloperidol is the nucleus accumbens. The reported data are well described by a neural network model of classical conditioning. This study contributes to the understanding of the neurophysiology of latent inhibition as well as the neuropsychological bases of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotoxic or electrolytic lesions of the ventral subiculum produce deficits in the acquisition and expression of Pavlovian fear conditioning in rats.

The effects of neurotoxic or electrolytic ventral subicular (vSUB) lesions on the acquisition and expression of Pavlovian fear conditioning in rats were examined. Conditioning consisted of the delivery of tone–footshock trials in a novel observation chamber, and freezing served as the measure of conditional fear. Pretraining vSUB lesions produced a severe tone freezing deficit and a modest context freezing deficit, whereas posttraining lesions produced severe deficits in freezing to both a tone -and a context conditional stimulus (CS). Similar impairments were produced by neurotoxic and electrolytic lesions. Increases in motor activity associated with the lesions could not account for freezing deficits. These results reveal that neurons in the vSUB have an important role in both the acquisition and expression of Pavlovian fear conditioning to contextual and acoustic CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mouse killing induced by para-chlorophenylalanine injections or septal lesions but not olfactory bulb lesions is similar to that of food-deprived spontaneous killers.

Compared mouse killing induced by septal lesions, olfactory bulb lesions, or parachlorophenylalanine (PCPA) injections in 21 rats with the behavior of 14 sated or 10 food-deprived spontaneous mouse-killing rats to evaluate whether the experimentally induced killing corresponded to killing that occurred spontaneously. On the 1st mouse kill, the intensity of the initial reaction to the mouse, the site of the initial attack, and the time required to kill by all groups were similar except that bulbectomized Ss required longer to kill. Following the kill, only Ss with septal lesions and bulbectomized Ss bit the mouse significantly more than spontaneous killers. With the 2nd mouse kill, there was an increase in the intensity of the response to the mouse and a decrease in attack latency by all groups except the bulbectomized Ss and the nondeprived spontaneous killers. When presented with a freshly killed mouse, Ss with septal lesions attacked with the greatest intensity, but PCPA-injected Ss and food-deprived spontaneous killers also attacked more intensely than nondeprived killers. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retention and acquisition of classical trace conditioned responses by rabbits with hippocampal lesions.

Examined the effects of dorsal hippocampal lesions on retention of classical trace conditioned responses (CRs) using the rabbit nictitating membrane preparation. In Exp I, 18 New Zealand albino rabbits were trained to criteria and then lesioned either in the cortex or in the hippocampus and the cortex. Hippocampal damage had no effect on the retention of responses but produced significantly longer onset latencies. A control group of hippocampal Ss acquired CRs at least as quickly as the prelesion Ss and exhibited longer response onset latency. Exp II, with 24 Ss, evaluated the performance of hippocampal-lesioned Ss in classical trace conditioning with either a low-intensity periorbital shock or a corneal air puff as the unconditioned stimulus (UCS). Hippocampal Ss successfully acquired CRs under both conditions but exhibited an alteration of response onset that depended on the form of the UCS. Hippocampal Ss displayed shorter response onset in the air-puff condition and longer response onset in the shock condition. Cortical Ss consistently timed responses regardless of the UCS. Findings suggest that the hippocampus modulates temporal characteristics of learned behavior. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning about categories that are defined by object-like stimuli despite impaired declarative memory.

Exposure to members of a category facilitates later categorization of similar but novel instances of the category. Past studies have suggested that category knowledge can be acquired implicitly and independently of declarative memory. However, these studies have relied on dot pattern stimuli that, unlike most real-world objects, are difficult to verbalize and cannot be broken into component features. It is therefore unclear how relevant such studies are to an understanding of everyday categorization. In the present studies, category learning in amnesic patients was tested with stimuli that both exhibit discrete features and are easy to describe (namely, cartoon animals). Amnesic patients were as competent as healthy volunteers in learning to categorize these animals, despite their impairment in recalling the animals' features. The results suggest that the implicit acquisition of category knowledge is a common process in everyday experience, and that it can occur whenever individuals encounter a large group of related items. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enzymatic activity of 2'-5'-oligoadenylate synthetase is impaired by specific mutations that affect oligomerization of the protein

Previous studies from our laboratory have shown that deletion of residues 321 to 344 of the 9-2 isozyme of 2'-5'-oligoadenylate (2-5(A)) synthetase causes a loss of its enzyme activity (Ghosh, S. K., Kusari, J., Bandyopadhyay, S. K., Samanta, H., Kumar, R., and Sen, G. C. (1991) J. Biol. Chem. 266, 15293-15299). Sequence comparison of this region among the different isozymes of 2-5(A) synthetases revealed that the residues at positions 330 to 333 are highly conserved. Alanine-scanning mutagenesis of these residues demonstrated that the residues present at 331, 332, and 333 are important for activity but the proline at position 330 was dispensable. The triple mutant containing Ala residues at 331, 332, and 333 was completely inactive. Different double mutants were slightly active, and the three single mutants were partially active. The triple mutant was further characterized for delineating the nature of its defect. The mutant protein was enzymatically inactive irrespective of whether it was synthesized in rabbit reticulocyte lysate, Escherichia coli or Trichoplusia ni insect cells. It could bind double-stranded RNA and ATP as efficiently as the wild type protein. It was, however, defective in oligomerization. Gel filtration and sedimentation velocity analyses of in vitro synthesized proteins revealed that the wild type protein, but not the triple mutant, formed tetramers. The tetrameric fraction, but not the monomeric fraction of the wild type protein was enzymatically active. The failure of the triple mutant to participate in homomeric protein-protein interaction was confirmed by in vivo assays in insect cells. These results indicate that tetramerization of the protein is required for the enzymatic activity of the small 2-5(A) synthetases.     

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

In rats with perifornical lateral hypothalamic (LH) electrodes that induced feeding, self-stimulation through the same electrodes increased immediately after ventromedial hypothalamic (VMH) lesions and did not return to normal until food intake normalized and the rats had become obese. A unilateral far-LH lesion decreased feeding and contralateral perifornical LH self-stimulation. 6-hydroxydopamine (6-OHDA) injected into the midbrain to destroy the ventral noradrenergic bundle (VNAB) caused hyperphagia and increased LH self-stimulation. In summary, VMH or VNAB damage increased feeding and self-stimulation; contralateral far-LH damage decreased both. Results confirm the earlier suggestion that the VMH region is necessary for normal inhibition of feeding and feeding reward as reflected in self-stimulation rate. Although massive 6-OHDA-induced depletion of the dopamine system that passes through the LH can cause starvation and impair self-stimulation, results suggest that selective catecholamine depletion of ventral midbrain neurons with sparing of the A9 and A10 dopaminergic cells can disinhibit feeding and self-stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Septal lesions in rats produce reversal deficits in a simultaneous visual discrimination.

Trained 54 rats with septal lesions and their operated controls on a 2-choice simultaneous brightness discrimination problem and its reversal using a correction procedure in a maze with 4 sequential choice points. Rats with septal lesions were deficient in the reversal of this brightness discrimination. However, this deficit was seen only in a measure of repeated errors and was considerably altered by forced preexposure to selected cues involved in discrimination. Thus, perseveration was seen, as measured by repeated errors, even though rats with lesions reached criterion in the same number of trials as operated controls. Findings emphasize the critical nature of stimulus conditions, response measures, and the history of the animal in determining the effects of brain damage on behavior. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual fear discrimination is impaired by damage to the postrhinal or perirhinal cortex.

Postrhinal (POR) or perirhinal (PER) cortex damage impairs acquisition and expression of contextual fear, but the nature of the impairment remains unclear. This study used a contextual fear discrimination paradigm that biased subjects toward using a configural, rather than an elemental, strategy to distinguish between 2 contexts, 1 of which was paired with a mild footshock. Control rats discriminated between 2 contexts when a combination of several cues could be used (Exp 1), but not when individual sensory cues were manipulated (Exp 2). Rats with POR or PER lesions could not discriminate between the shock and no-shock contexts when multiple cues differentiated the contexts (Exp 3). The results indicate that both the POR and PER have a role in configural learning of contextual fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paraventricular hypothalamic lesions and medial hypothalamic knife cuts produce similar hyperphagia syndromes.

Compared the hyperphagia/obesity syndrome produced by paraventricular hypothalamic (PVH) lesions and that produced by medial hypothalamic (MH) knife cuts in adult female Sprague-Dawley rats. Each treatment produced hyperphagia and overweight on a chow diet, although the PVH effect was less than the knife cut effect. Each treatment also produced qualitatively similar ingestive responses to unpalatable quinine- and sucrose octaacetate-adulterated diets and to palatable dextrose and fat diets during the dynamic and static weight-gain phases. The PVH lesions and MH cuts disrupted day/night feeding patterns and elevated water intakes but not water/food intake ratios. However, PVH lesions, unlike MH cuts, did not increase emotional reactivity. The relation of the PVH syndrome to the classic hypothalamic hyperphagia syndrome is discussed. Also considered is the neuroanatomical substrate responsible for the PVH hyperphagic effect. (66 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carotid body chemoreceptor function is impaired by vecuronium during hypoxia

BACKGROUND: Neuromuscular blocking agents reduce the human ventilatory response to hypoxia at partial neuromuscular block. It was hypothesized that vecuronium impairs carotid body chemoreceptor function during hypoxia. METHOD: The effect of systemic administration of vecuronium on single chemoreceptor activity during hypoxia, as recorded from a single nerve fiber preparation of the carotid sinus nerve, was studied in seven mechanically ventilated New Zealand White rabbits during continuous thiopental anesthesia. During normoventilation, the isocapnic hypoxic chemosensitivity of the single carotid body chemoreceptor was measured at four levels of oxygenation; these measurements were repeated at six separate occasions: control recording before injection, after intravenous administrations of 0.1 mg and 0.5 mg of vecuronium, and then at three occasions during a 90-min recovery period. Chemoreceptor chemosensitivity during isocapnic hypoxia was expressed as a hyperbolic function: Chemoreceptor output (Hz) = a + b x PaO2(-1) (mmHg). RESULTS: Chemosensitivity was reduced after both 0.1 mg and 0.5 mg vecuronium intravenous administration compared with control measurements; the hypoxic response curve was significantly depressed after both doses (P < 0.05). Notably, there was variation in the effect of vecuronium; some chemoreceptor preparations showed only minimal impairment, whereas some showed an almost abolished response to hypoxia. The chemosensitivity remained significantly depressed at 30 and 60 min but had recovered spontaneously at 90 min after 0.5 mg vecuronium. DISCUSSION: It is concluded that vecuronium depresses carotid body chemoreceptor function to a varying extent during hypoxia and that the depression recovers spontaneously.     

Evidence from comparative investigations that impaired platelet activation is not specific for stroke-prone spontaneously hypertensive rats

BACKGROUND AND PURPOSE: Platelet behavior of Sprague Dawley (SD), Wistar (WI), Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive rats (SHRSP) was studied in vivo to evaluate the importance of hypertension-related hemostatic disorders. METHODS: The study was based on the model of stimulus-induced pulmonary microembolization of labeled platelets. After injection of 51Cr-labeled homologous platelets into urethane-anesthetized rats, the organ distribution of the platelets was continuously monitored by gamma detectors. Count rates of two detectors--one placed above the animals' thoraxes (C1), the other above their abdomens (C2)-and the ratio of C1:C2 were calculated. The following platelet activators were applied intravenously: adenosine diphosphate (ADP; 50 micrograms/kg), collagen (100 micrograms/kg), and thrombin (50 IU/kg). RESULTS: All three substances caused a reversible pulmonary accumulation of the labeled platelets and hence an increase in C1/C2 (delta C1/C2%). ADP induced a shift of 75% in SD, 52% in WI, 32% in WKY, 30% in SHR, and 31% in SHRSP. Thrombin-mediated shift was 79% in SD, 64% in WI, 58% in WKY, 48% in SHR, and 54% in SHRSP. Collagen induced a shift of 85% in SD, 96% in WI, 84% in WKY, 56% in SHR, and 62% in SHRSP. CONCLUSIONS: Because indistinguishable results were observed in both hypertensive strains, we conclude that impaired platelet aggregation is not specific for SHRSP. Hence, it may not primarily be responsible for the increased occurrence of stroke in these animals.     

On finding that speech is special.

Determined how speech is able to communicate phonological segments by sounds. Is was found that specialized processes of phonetic perception had been made to conform to the acoustic consequences of the way articulatory movements are regulated. The distinctively linguistic function of these specializations is to provide for efficient perception of phonetic structures that can also be efficiently produced. To assume that a phonetic specialization exists accords well with a "vertical" view of language (rather than the "horizontal" view expected), in which the underlying activities are seen as coherent and distinctive. Recent evidence for such special processes comes from experiments designed to investigate the integration of cues (e.g., B. H. Repp et al; see record 1980-22645-001). (60 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term habituation to repeated loud noise is impaired by relatively short interstressor intervals in rats.

The phenomenon of spaced (longer intertrial interval) compared with massed (shorter intertrial interval) training leading to better long-term habituation and associative learning is well documented. However, the effects of intertrial intervals on response habituation to repeated stress exposures have not been previously examined. The present experiments found that massed (six 30-min exposures of 95 dB white noise in 6 hr) and spaced (one 30-min exposure daily for 6 days) noise exposures led to similar habituation of plasma corticosterone and ACTH responses, heart rate, and core body temperature after the 6th exposure in male Sprague-Dawley rats. However, these habituated responses were not retained in the massed group on a similar noise re-exposure 48 hr later, compared with the spaced group. The habituated responses found in the massed group after the 6 noise exposures were not due to differential hearing threshold shifts, as examined with modifications of the acoustic startle reflex. These data indicate that relatively short interstressor intervals impair long-term stress adaptation. This series of studies supports the idea of distinct short- and long-term habituation processes to stress responsiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motor skills have diverse neural bases: Spared and impaired skill acquisition in Huntington's disease.

The striatum contributes to the learning of some, but not all, motor skills. The researchers suggest that the striatum plays a role when participants learn a repeating sequence of movements, but it does not contribute when they learn a new mapping between perceptual cues and the appropriate motor response. The researchers tested patients with striatal damage due to Huntington's disease (HD) on 2 versions of a tracking task. In 1 task, the target moved randomly, allowing participants to learn the relationship between the joystick and cursor. Patients showed normal learning. In the other task, the target moved in a repeating pattern, and participants could improve performance by learning the repeating sequence of movements necessary to track the pattern. Patients were impaired on this task. Learning sequences is impaired in HD, whereas learning new mappings between perceptual cues and responses is not. (PsycINFO Database Record (c) 2010 APA, all rights reserved)