Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine tegmental nucleus.

Prepulse inhibition (PPI) of startle is impaired in schizophrenics, which suggests they have disturbances in circuitry that controls PPI. How activity in forebrain circuitry is communicated to the primary startle circuit to modulate PPI was explored. Subpallidal cells innervate the pedunculopontine tegmental nucleus (PPTg). Infusion of the γ-aminobutyric acid antagonist picrotoxin into the subpallidum impaired PPI. In other rats, electrolytic PPTg lesions decreased or eliminated PPI, potentiated startle amplitude, and did not alter habituation. The disruption of PPI correlated significantly with the extent of PPTg damage. PPTg lesions reduced PPI when startle stimuli were weak or intense (104 or 140 db) and when prepulse stimuli ranged from 2 to 17 db above background but were most profound with prepulses 5–8 db above background. The PPTg modulates sensorimotor gating and may process and transmit information from forebrain structures to the primary startle curcuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Goal-directed selective attention and response competition monitoring: Evidence from unilateral parietal and anterior cingulate lesions.

Competing visual stimuli lead to slower responses to targets. This response competition must be resolved before correct responses are executed. Neuroimaging suggests that response competition monitoring may be subserved by an integrated neural network including the anterior cingulate cortex (ACC). In this study, 1 patient with a parietal lesion (Patient J.S.) and 1 with an ACC lesion (Patient G.M.) were presented with 2 flanker tasks; 1 required verbal identification of color targets, and the other required an opposite response to targets (e.g., see red and say "green"); a control group was also tested. For controls, perceptually incongruent flankers interfered with the ability to inhibit prepotent responses to targets. Patient J.S. performed in a similar manner, even when flankers appeared in the neglected field. Patient G.M. demonstrated reduced interference effects for contralesional flankers. Results are discussed in terms of goal-directed selective attention and response competition monitoring. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for a role of dopamine in self-stimulation of the nucleus accumbens of the rat.

Investigated the effects of centrally administered spiroperidol, a dopamine receptor blocking agent, on self-stimulation of the nucleus accumbens and medial prefrontal cortex in the rat. Spiroperidol in a volume of 1 μl was microinjected into the region of the stimulating electrodes. Self-stimulation of the nucleus accumbens was significantly attenuated by .75, 1.0, and 2.0 μg spiroperidol. Control microinjections of the drug vehicle had no effect. Spiroperidol microinjected into the nucleus accumbens contralateral to the stimulating electrode, as a control for possible motor or nonspecific effects, did not attenuate self-stimulation. Microinjections of spiroperidol into the region of the stimulating electrodes in the prefrontal cortex had no consistent effect on self-stimulation with the two lower doses, but did result in attenuation at the 2.0 μg dose. Self-stimulation of the nucleus accumbens was not changed by microinjections of spiroperidol into the ipsilateral or contralateral prefrontal cortex. Similarly, self-stimulation of the prefrontal cortex was not altered by microinjections of spiroperidol into the nucleus accumbens. By controlling for nonspecific effects of spiroperidol, the results provide further evidence that dopaminergic neurons contribute to self-stimulation of the nucleus accumbens. (French summary) (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synaptic integration of functionally diverse pallidal information in the entopeduncular nucleus and subthalamic nucleus in the rat

To determine the principles of synaptic innervation of neurons in the entopeduncular nucleus and subthalamic nucleus by neurons of functionally distinct regions of the pallidal complex, double anterograde labeling was carried out at both light and electron microscopic levels in the rat. Deposits of the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine were placed in different functional domains of the pallidal complex in the same animals. The tracer deposits in the ventral pallidum and the globus pallidus gave rise to GABA-immunopositive projections to the entopeduncular nucleus, the subthalamic nucleus, and the more medial lateral hypothalamus that were largely segregated but overlapped at the interface between the two fields of projection. In these regions the proximal parts of individual neurons in the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus received synaptic input from terminals derived from both the ventral pallidum and the globus pallidus. Furthermore, the analysis of the afferent synaptic input to the dendrites of neurons in the subthalamic nucleus that cross functional boundaries of the nucleus defined by the pallidal inputs, revealed that terminals with the morphological and neurochemical characteristics of those derived from the pallidal complex make synaptic contact with all parts of the dendritic tree, including distal regions. It is concluded that functionally diverse information carried by the descending projections of the pallidal complex is synaptically integrated by neurons of the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus by two mechanisms. First, neurons located at the interface between functionally distinct, but topographically adjacent, projections could integrate diverse information by means of the synaptic convergence at the level of the cell body and proximal dendrites. Second, because the distal dendrites of neurons in the subthalamic nucleus receive input from the pallidum, those that extend across two distinct domains of pallidal input could also provide the morphological basis of integration.     

Ipsiversive progression and unilateral posterior cortical lesions in the rat.

Hypothesized that nonvisual deficits ascribed to visual cortex lesions reflect an impairment in spatial progression. To evaluate this possibility, 64 male hooded rats were enucleated, subjected to unilateral neocortical lesions, and tested for ipsiversive progression. The hypothesis was not supported since destruction of the visual cortex alone did not produce the effect while similar-sized, more anteriorly placed, lesions did. Moreover, there was nothing to indicate that visual cortex destruction in combination with an effective lesion enhanced the effect. Results support those who have criticized the belief that the visual cortex carries out nonvisual functions. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)

Recent studies in non-human primates support a role for the subthalamic nucleus in the expression of parkinsonian symptomatology, and it has been proposed that subthalamic lesions may provide a surgical treatment for the symptoms of Parkinson's disease in humans. We have applied a broad range of behavioural tests to characterize the effects of lesions of the subthalamic nucleus on parkinsonian symptoms in the unilateral 6-hydroxydopamine (6-OHDA) lesioned marmoset (Callithrix jacchus). Thirteen marmosets were trained on a battery of behavioural tasks that were conducted at regular intervals before and after surgery. All received unilateral 6-OHDA lesions to the medial forebrain bundle. Seven animals were then given an additional N-methyl-D-aspartate lesion of the ipsilateral subthalamic nucleus, whereas the remaining six animals received a variety of control or sham lesions to the nucleus. The 6-OHDA lesions induced a strong ipsilateral bias in head position; mild-moderate ipsilateral rotation spontaneously and after injection of saline or amphetamine; and contralateral rotation after injection of apomorphine. Hemineglect was evident as delayed initiation of reaches on the contralateral side on the staircase reaching task. Additional subthalamic lesions significantly reversed the bias in head position from ipsilateral to contralateral and decreased neglect as evidenced by improved latencies to initiate reaching on the contralateral side at the staircase. However, deficits in skilled movements persisted in the subthalamic nucleus lesion group in that they did not complete the staircase task any faster than the control group and remained impaired on another task which required reaching into tubes. These behavioural effects demonstrate that excitotoxic lesioning of the subthalamic nucleus can ameliorate some, but not all, parkinsonian-like deficits in the unilateral 6-OHDA lesioned marmoset.     

Tactile extinction following unilateral lesions in the rat anteromedial cortex: Effects of a contralateral cue.

Following unilateral lesions of the anteromedial cortex (AMC) or the caudal forelimb representation (CFL), rats prefer to remove an adhesive patch placed on the forelimb ipsilateral to the lesion before removing a simultaneously applied contralateral patch (i.e., ipsilateral asymmetry). The present experiment was designed to investigate the possibility that attention has some role in these asymmetries. Specifically, the researchers investigated whether a contralateral tactile cue presented before the simultaneous presentation of bilateral tactile stimuli would neutralize the ipsilateral asymmetry. In 14 male rats with AMC lesions, the contralateral cue neutralized the ipsilateral bias, whereas the cue had no effect on 6 male rats with CFL lesions. These data suggest that the ipsilateral bias observed in AMC-damaged rats may reflect an impairment in attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of unilateral parietal lesions on spatial localization in the rat.

In the 1st of 2 experiments, rats with left or right parietal lesions and controls were tested in place and landmark navigation in the water maze. Right parietal lesions resulted in deficits in both tasks, but especially landmark navigation. Lateralized effects appeared mainly in latency to find the platform. Exp 2 investigated the role of the corpus callosum. Split-brain rats with unilateral parietal lesions were tested on the same 2 tasks. Place and landmark deficits were particularly severe, but lateralization was weaker. Callosum section had its own effect, impairing the learning of both tasks. There appear to be additive effects of unilateral cortical lesions and bisection of the hemispheres. The impairment from left lesions equaled the right-lesion deficit because of the interruption of compensatory information from the intact right hemisphere and the effect of callosum section itself. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The subthalamic nucleus: a possible target for stereotaxic surgery in Parkinson''s disease

Agenesis of the sacrum is a rare anomaly that is associated with numerous visceral abnormalities, spinal cord malformation, and lower limb defects. A fatal case of sacral and lower lumbar agenesis in a 3-day-old female infant born at 38 weeks of gestation is reported. The extraneural malformations comprised an imperforate anus, a rectovaginal fistula, and musculoskeletal abnormalities, including several thoracocervical hemivertebrae and aplasia of the sacrum and the fourth and fifth lumbar vertebrae. The cervical and high thoracic spinal cord segments were normal. Disruption of secondary neurulation, possibly due to notochord dysfunction, was suggested by malformation of the ventral half of the lower thoracic spinal cord with relative preservation of the dorsal horns and, more caudally, by loss of all normal histological landmarks, including the central canal. Neither skeletal muscle nor myoblasts were found in muscle compartments that would normally have received motor innervation from the levels of the spinal cord from which anterior horn cells were absent, indicating parallel, segmental failure of myotomal differentiation in the caudal eminence.     

Impaired sexual response after lesions of the paraventricular nucleus of the hypothalamus in male rats

N-methyl-D-aspartic acid (NMDA) or radiofrequency (RF) lesions were made in the paraventricular nucleus of the hypothalamus (PVH) of male rats. The rats were tested for copulation, noncontact erection (NCE) evoked by remote cues from estrous females, and (after RF lesions) reflexive erection. NMDA, which destroyed parvocellular but spared magnocellular neurons, caused no deficits in copulation but caused longer NCE latencies and fewer NCEs. Rats with RF lesions had parvo- and magnocellular neuron damage; these males copulated to ejaculation, but they had lower intromission ratios and longer ejaculatory latencies. RF-lesioned rats also had longer NCE latencies, and a smaller proportion of males displayed reflexive erection. Results indicate that the PVH participates in mediating erectile function in copula and ex copula, and that the parvo- and magnocellular PVH neurons may have different roles in mediating erection.     

Medial prefrontal lesions in the rat and spatial navigation: Evidence for impaired planning.

Rats with medial prefrontal cortical lesions were tested in a modified water maze navigation task. In Stage 1, the rats were trained to locate a hidden platform from a single start location. They were then subjected to a series of trials during which a second start position was used (Stage 2). In Stage 3, the rats had to navigate to a new goal location from the 2 experienced start positions. Stage 4 required the rats to navigate to the same goal as in Stage 3, starting from 4 distinct positions. Finally, a single probe trial with no platform was conducted. Rats with prefrontal lesions were impaired only during Stage 4. This deficit was specific to the 2 start positions newly introduced during this stage, suggesting a dysfunction of planning processes. This impairment might result from a working memory deficit, precluding the animal from forming an adequate representation of the whole course of movements required to reach the platform. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat

The effect of cannabinoids on the excitatory input to the substantia nigra reticulata (SNr) from the subthalamic nucleus was explored. For this purpose a knife cut was performed rostral to the subthalamic nucleus to isolate the subthalamic nucleus and the SNr from the striatum, a major source of cannabinoid receptors to the SNr. The data showed that the cannabinoid agonist WIN55,212-2 blocked the increase in the firing rate of SNr neurons induced by stimulation of the subthalamic nucleus with bicuculline. Furthermore, the cannabinoid antagonist SR141716A antagonized the effect of the cannabinoid agonist. This study showed that cannabinoids regulate not only the striatonigral pathway, as previously reported, but also the subthalamonigral pathway. The opposite influences of these two inputs to the SNr, inhibitory and excitatory respectively, suggest that endogenous cannabinoids play a major role in the physiological regulation of the SNr.     

Sound localizations after kainic acid lesions of the dorsal nucleus of the lateral lemniscus in the albino rat.

The ability of rats to localize sounds in space was determined before and after kainic acid lesions of the dorsal nucleus of the lateral lemniscus (DNLL). The rats were trained to approach a 45-msec noise burst delivered from loudspeakers on the right or left of midline. Lesions were made by local injection of kainic acid into the DNLL. Rats with unilateral lesions of DNLL were impaired in their postoperative ability to localize a single noise burst. Rats with bilateral lesions also had deficits in postoperative performance, but the severity of the impairment was not substantially greater than that expected from a unilateral lesion. The mean pre- and postoperative minimum audible angles were 14.8° and 40.4° for rats with complete unilateral lesions and 13.5° and 36.0° for rats with bilateral lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visual cortical lesions in the rat and a conditioned emotional response.

Reports results of 11 experiments with Long-Evans rats (N = 105). Visual decortication failed to affect rate of acquisition of 1-min delayed CERs when either light alone or noise alone provided the CS. However, CER paradigms involving a combination of light and noise CSs revealed differences in behavior between experimental and control Ss. Decorticate Ss transferred the CER from light to noise (although not from noise to light); normal Ss showed no transfer. Decorticate Ss were conditioned to a noise CS in a paradigm which prevented conditioning in normal Ss. Also, decorticate Ss were better able to discriminate a compound light-noise CS from light-alone and noise-alone CS. Based on the findings and the fact that abnormal behavior of the decorticate Ss was mimicked by normal Ss wearing light-diffusing eye occluders, it is speculated that vision as a qualitatively unique sensory modality is undermined by visual cortex destruction. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Muscarinic cholinoceptor subtypes in the rat frontoparietal cortex after ipsilateral lesions of the nucleus basalis magnocellularis

Muscarinic cholinoceptor subtypes (M1 and M2) were studied in membrane particles of the rat frontoparietal cortex 72 h and 1, 2, 3, and 4 weeks after ipsilateral lesioning of the nucleus basalis magnocellularis (NBM). The affinity of the ligand used to characterize muscarinic cholinoceptors, 3H-quinuclidinyl benzilate did not significantly change in lesioned compared with sham-operated rats as well as the density of high affinity (M1) sites. Low affinity muscarinic cholinoceptors (M2 sites) were significantly decreased in NBM-lesioned rats 72 h and 1 week after lesioning. The density of M2 sites did not significantly differ in lesioned rats 2 or 3 weeks after NBM lesioning, but increased, in comparison with sham-operation 4 weeks after NBM lesioning. These findings suggest that frontoparietal M2 muscarinic cholinoceptors, which probably have a presynaptic localization, are sensitive to NBM lesions. Their changes at different times after NBM lesioning suggest the occurrence of loss, compensation and upregulation of cholinergic projections arising to the neocortex from the NBM.     

Parabrachial nucleus lesions and conditioned taste aversion: Evidence supporting an associative deficit.

Three experiments examined the conditioned taste aversion (CTA) deficit that occurs following electrolytic lesions of the parabrachial nucleus (PBN). In Exp 1, lesioned rats failed to avoid either a gustatory or an olfactory stimulus that had been paired with lithium chloride-induced toxicosis. In Exp 2, however, all rats learned a conditioned flavor preference. Finally, in Exp 3, all controls and 7 of the 12 lesioned rats learned a conditioned place aversion. Together, these results demonstrate that the disruption of CTA in lesioned rats cannot be ascribed to an inability to process either gustatory or visceral afferent information per se. Rather, the data suggest that PBN-lesioned rats are unable to form a specific association between gustatory and visceral cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociating consciousness from inhibitory control: Evidence for unconsciously triggered response inhibition in the stop-signal task.

Theories about the functional relevance of consciousness commonly posit that higher order cognitive control functions, such as response inhibition, require consciousness. To test this assertion, the authors designed a masked stop-signal paradigm to examine whether response inhibition could be triggered and initiated by masked stop signals, which inform participants to stop an action they have begun. In 2 experiments, masked stop signals were observed to occasionally result in full response inhibition as well as to yield a slow down in the speed of responses that were not inhibited. The magnitude of this subliminally triggered response time slowing effect correlated with the efficiency measure (stop signal reaction time) of response inhibition across participants. Thus, response inhibition can be triggered unconsciously—more so in individuals who are good inhibitors and under conditions that are associated with efficient response inhibition. These results indicate that in contradiction to common theorizing, inhibitory control processes can operate outside awareness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-lasting increase in anxiety after electrolytic lesions of the pedunculopontine tegmental nucleus.

This study examined the effect of electrolytic lesions of the pedunculopontine tegmental nucleus (PPTg) on emotionality in rats. Rats with PPTg or sham lesions were tested in the elevated plus-maze, the social interaction test, the open-field test, and the conditioned fear paradigm. Histology showed that lesions were concentrated on the caudal half of the PPTg. In the plus-maze, behavioral scores were biased toward increased "anxiety" on the 1st testing day. Five consecutive exposures to the apparatus led to marked habituation in sham-lesioned but not in PPTg-lesioned rats. On the 5th day, most indexes of emotionality indicated elevated anxiety in PPTg-lesioned rats. Increased anxiety was also found in PPTg-lesioned rats in the social interaction test. In the conditioned fear paradigm, movement suppression during the postconditioned stimulus period was found in both groups on the 1st day of extinction but only in PPTg-lesioned rats on the 2nd extinction day, indicating extinction was slower in PPTg-lesioned rats. Lesions of the caudal PPTg appear to produce long-lasting anxiety in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitation of rat subthalamic nucleus neurones in vitro by activation of a group I metabotropic glutamate receptor

The subthalamic nucleus (SThN) provides a glutamate mediated excitatory drive to several other component nuclei of the basal ganglia, thereby significantly influencing locomotion and control of voluntary movement. We have characterised functionally the metabotropic glutamate (mGlu) receptors in the SThN using extracellular single unit recording from rat midbrain slices. SThN neurones fired action potentials spontaneously at a rate of 10 Hz which was increased by the group I/II mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3 R-ACPD; 1-30 microM) and the group I selective agonist (S, R)-dihydroxyphenylglycine (DHPG; 1-30 microM). However, both the group II selective agonist (1S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 1 microM) and the group III selective agonist (S)-2-amino-4-phosphonobutanoic acid (L-AP4; 10 microM) were without effect, indicating that the excitation was mediated by a group I mGlu receptor. The excitation caused by DHPG (3 microM) was reversed by co-application of the mGlu receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 500 microM). Thus a group I mGlu receptor mediates excitation of SThN neurones, and suggests a use for group I mGlu receptor ligands for treatment of both hypo- and hyperkinetic disorders of basal ganglia origin, such as Parkinson's disease and Huntington's disease.