Effects of reversible inactivation of thalamo-striatal circuitry on delayed matching trained with retractable levers

The intralaminar thalamic nuclei are characterized by their prominent projections to striatum. Lesions of the intralaminar nuclei have been found to impair delayed matching trained with retractable levers. Comparable impairments have been observed for rats with lesions of the olfactory tubercle, involving ventral areas of striatum and pallidum. We conducted two experiments to test the functional dependence of thalamic and striatal lesions on the delayed matching task. In experiment 1, we determined the effects of inactivating the intralaminar nuclei with bilateral lidocaine infusions. In experiment 2, we compared the effects of unilateral thalamic inactivations in rats with unilateral olfactory tubercle lesions. We trained rats to perform the delayed matching task to criterion and then implanted dual cannulas aimed at the bilaterally symmetrical areas in the intralaminar nuclei. Rats in experiment 2 were also given a unilateral olfactory tubercle lesion. The results of experiment 1 showed dose-dependent impairments for bilateral infusions that were qualitatively similar, although of lesser severity than delayed matching impairments observed in previous studies for rats with lesions involving extensive areas of the intralaminar nuclei. A comparable impairment was observed in experiment 2 when thalamus was inactivated on the side opposite the olfactory tubercle lesion. Performances were significantly worse when thalamus was inactivated on the contra-lesion than on the ipsi-lesion side of the brain. These results are discussed in terms of the role of ventral striatum and related thalamic nuclei in memory.     

Effects of rat ventral and dorsal hippocampus temporal inactivation on delayed alternation task

To determine the involvement of the hippocampal regions in a operant-type delayed alternation task of short delay or long delay, microinjections of muscimol into the hippocampus were used for temporal inactivation during the behavioral test in each rat. Dorsal hippocampal inactivation impaired the correct ratio of long delay. Ventral hippocampal inactivation showed no changes in the correct ratio, however, it increased the tendency of perseveration in long delay. These findings suggest hippocampus has regional differentiation in delayed alternation task.     

Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors in rats

This study investigated the role of the hippocampus in both unconditioned and conditioned defensive behaviors by examining the effects of pretraining ibotenic acid lesions to the dorsal and ventral hippocampus in male Long-Evans hooded rats exposed to three types of threat stimuli: cat-odor, a live cat and footshock. Defensive behaviors were assessed during exposure to cat-odor and a live cat, and immediately following the presentation of footshock. Conditioned defensive behaviors were also assessed in each context 24 h after initial threat exposure. During both unconditioned and conditioned trials, dorsal hippocampal lesions failed to significantly alter any behavioral measure in each test of defense. In contrast, ventral hippocampal lesions significantly reduced unconditioned defensive behaviors during exposure to cat-odor without producing any observable effects during cat exposure. Furthermore, ventral lesions significantly attenuated conditioned defensive behaviors following the administration of footshock and during re-exposure to each context. These results suggest a specific role for the ventral, not dorsal, hippocampus in modulating anxiety-like behaviors in certain animal models of defense.     

Effects of ventral striatal lesions on first‐ and second‐order appetitive conditioning

Rats with bilateral lesions of the ventral striatal nucleus accumbens failed to acquire Pavlovian second‐order conditioning to auditory stimuli paired with visual stimuli that had previously received first‐order pairings with food. This deficit in second‐order conditioning was specific to learning driven by incentive properties of the first‐order cues, and was observed whether the first‐order training had occurred prior to or after lesion surgery. Lesions also produced deficits in the display of conditioned responses to the first‐order conditioned stimulus, but only when they were made after first‐order training. These results suggest a specific role for the ventral striatum in acquiring and expressing incentive properties of conditioned stimuli through second‐order conditioning, as well as a more general role in expressing previously acquired Pavlovian conditioned responses.     

Differential effects of kainic acid on dopamine and serotonin metabolism in ventral and dorsal striatal regions

The comparative effects of kainic acid (KA) on dopamine (DA) and serotonin (5-HT) metabolism in ventral and dorsal striatum were investigated. Local injection of KA into the caudate-putamen (CP) increased by 155% DOPAC (2,3-dihydrophenylacetic acid), by 114% HVA (homovanillic acid) and by 79% 5-HIAA (5-hydroxyindoleacetic acid) concentrations: with little or no effect on monoamine levels. The (DOPAC + HVA)/DA ratio increased from 0.33 ± 0.2 in vehicle-treated to 0.77 ± 0.1 in KA-treated CP. 5-HIAA/5-HT ratio increased from 2.7 ± 0.2 to 5.9 ± 0.1 after KA treatment. However, direct KA injections into the olfactory tubercle (OT), the most ventral part of the ventral striatum, did not alter significantly the levels of DA, 5-HT, DOPAC, HVA or 5-HIAA. Since KA is a neurotoxin which preferentially destroys perykaria and dendrites, leaving unchanged terminal boutons and axons of passage, the lack of effects on DA and 5-HT metabolism in OT suggests, that contrary to the CP, interneurons and projecting neurons in the OT play no role in inhibitory feedback mechanisms to control DA and 5-HT activities.     

Superior temporal lesions and delayed auditory matching in monkeys

This study considers whether or not unilateral removal of superior temporal cortex in monkeys disrupts performance of a nonspatial delayed auditory matching task. Preliminary evidence of such an impairment has been suggested. Monkeys were evaluated before and after unilateral and serial bilateral removal of superior temporal cortex. No significant postoperative impairment was noted.     

Effects of dorsal or ventral medial prefrontal cortical lesions on five-choice serial reaction time performance in rats

Lesions of the rat medial prefrontal cortex (mPFC) produce behavioral impairments in the 5-choice serial reaction time (5CSRT) task, a widely used measure of sustained and selective visual attention. This experiment compared the effects of “dorsal” (centered on prelimbic and infralimbic cortices) and “ventral” (centered on dorsal peduncular cortex and tenia tecta) mPFC lesions on performance in a variant of the 5CSRT task. Because in some associative learning theories, the predictive validity of events determines the allocation of attention to them, we also examined the effects of cue validity in this task. Operant nosepoke responses to some briefly illuminated ports were consistently (100%) reinforced (CRF) with food, whereas for other ports, responding was reinforced on only 50% of the trials (partial reinforcement, PRF). Different patterns of impairment emerged depending on lesion location within the mPFC. Dorsal- and sham-lesioned rats responded more to CRF than to PRF cues, but ventral-lesioned rats responded similarly to CRF and PRF cues. Additionally, under some conditions of increased attentional demands, dorsal-lesioned rats failed to respond on many trials, whereas the impairment in ventral-lesioned rats was manifested as an increase in response errors. These results demonstrate separable roles for dorsal and ventral mPFC subregions in controlling attention.     

Differential response of ventral midbrain and striatal progenitor cells to lesions of the nigrostriatal dopaminergic projection

In response to injury, progenitor cells in the adult brain can proliferate and generate new neurons and/or glia, which may then participate in injury-induced compensatory processes. In this study, we explore the ability of young adult mice to generate new cells in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions, which selectively kill nigrostriatal dopaminergic neurons. Using the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), we labeled dividing cells 3, 10, and 15 days after MPTP lesion. A robust proliferative response was seen specifically in the substantia nigra (SN) and the dorsal striatum 3 days postlesion; the response persisted 10-14 days. To explore the fate of proliferative cells, we administered BrdU 3 days postlesion and examined the phenotype of BrdU(+) cells at various times thereafter, using double immunolabeling. In the striatum, nearly all newly-generated cells rapidly differentiated into GFAP(+) astrocytes that participated in the injury-induced glial reaction. In the SN, however, reactive astroglia were not BrdU(+). Some midbrain cells co-immunostained for BrdU and Mac-1, a microglial marker. However, most BrdU(+) cells in the SN failed to express markers for microglia, astroglia, oligodendroglia, or neurons, suggesting that they may remain as uncommitted progenitors. Thus, progenitors in the vicinity of the degenerating dopaminergic cell bodies respond differently to lesion than progenitors in the vicinity of the degenerating axon terminal. Although the putative midbrain progenitors appear uncommitted 22 days after their birth, it is possible that they may adopt neural or glial fates if allowed to survive longer, or if exposed to exogenous factors.     

Anatomical correlates of locomotor recovery following dorsal and ventral lesions of the rat spinal cord

The present study was designed to relate functional locomotor outcome to the anatomical extent and localization of lesions in the rat spinal cord. We performed dorsal and ventral lesions of different severity in 36 adult rats. Lesion depth, spared total white matter, and spared ventrolateral funiculus were compared to the locomotor outcome, assessed by the BBB open-field locomotor score and the grid walk test. The results showed that the preservation of a small number of fibers in the ventral or lateral funiculus was related to stepping abilities and overground locomotion, whereas comparable tissue preservation in the dorsal funiculus resulted in complete paraplegia. The strongest relation to locomotor function was between the BBB score and the lesion depth as well as the BBB score and the spared white matter tissue in the region of the reticulospinal tract. Locomotion on the grid walk required sparing in the ventrolateral funiculus and additional sparing of the dorsolateral and dorsal funiculus, where the cortico- and rubrospinal tracts are located.     

Visual illusions, delayed grasping, and memory: no shift from dorsal to ventral control

We tested whether a delay between stimulus presentation and grasping leads to a shift from dorsal to ventral control of the movement, as suggested by the perception-action theory of Milner and Goodale (Milner, A.D., & Goodale, M.A. (1995). The visual brain in action. Oxford: Oxford University Press.). In this theory the dorsal cortical stream has a short memory, such that after a few seconds the dorsal information is decayed and the action is guided by the ventral stream. Accordingly, grasping should become responsive to certain visual illusions after a delay (because only the ventral stream is assumed to be deceived by these illusions). We used the Müller-Lyer illusion, the typical illusion in this area of research, and replicated the increase of the motor illusion after a delay. However, we found that this increase is not due to memory demands but to the availability of visual feedback during movement execution which leads to online corrections of the movement. Because such online corrections are to be expected if the movement is guided by one single representation of object size, we conclude that there is no evidence for a shift from dorsal to ventral control in delayed grasping of the Müller-Lyer illusion. We also performed the first empirical test of a critique Goodale (Goodale, M.A. (2006, October 27). Visual duplicity: Action without perception in the human visual system. The XIV. Kanizsa lecture, Triest, Italy.) raised against studies finding illusion effects in grasping: Goodale argued that these studies used methods that lead to unnatural grasping which is guided by the ventral stream. Therefore, these studies might never have measured the dorsal stream, but always the ventral stream. We found clear evidence against this conjecture.     

Bladder rehabilitation with dorsal rhizotomy and ventral neuroprosthesis.

Two patients with severe neuropathic bladders were successfully treated with selective dorsal rhizotomy in conjunction with a ventral root neuroprosthesis. Both patients achieved stabilization of their renal function, continence, resolution of vesicoureteral reflux, and relief from indwelling urethral catheters. This alternative form of management avoids the complications of other operative approaches.     

Effects of amygdala lesions on dorsal hippocampus kindling in rats

In two experiments, bilateral amygdala lesions were shown to facilitate the rate of kindling from the dorsal hippocampus. This facilitation was produced equally by an amygdala lesion ipsilateral to the kindled focus, whereas a lesion contralateral to the focus was ineffective. An interesting negative correlation emerged between the kindling rate and latency to onset of forelimb clonus, i.e., the faster the kindling, the longer the convulsion latencies.     

Effects of lesions in the amygdala and periventricular hypothalamus on striatal somatostatin-like immunoreactivity

Somatostatin has been found in substantial amounts in the basal ganglia by radioimmunoassay and has been demonstrated in both neurons and nerve terminals. Since the levels of somatostatin have been shown to vary in Huntington's and Alzheimer's disease it was of interest to see whether such changes could be produced experimentally. Lesions of the periventricular nucleus of the hypothalamus and knife cuts adjacent to this nucleus had no effect on striatal somatostatin-like immunoreactivity (SLI). Similarly lesions of mediodorsal frontal cortex, and those isolating pyriform cortex or the olfactory bulb had no effect on striatal SLI. Removal of tge amygdala resulted in significant increases in SLI in the ipsilateral striatum and nucleus accumbens, suggesting loss of an inhibitory interaction. Stria terminalis lesions failed to reproduce this effect suggesting that it is mediated via amygdalo-striatal projections traveling in the dorsal longitudinal bundle. Other findings support a somatostatin projection to the amygdala from the bed nucleus of the stria terminalis and one from the amygdala to the ventromedial hypothalamus.     

Effects of lesions in ventral anterior thalamus on experimental focal epilepsy

The effect of stereotaxic lesions of the ventral anterior thalamus, or the adjacent inferior thalamic peduncle, on experimental models of focal cortical epilepsy was studied. Acute epileptic foci in cat sensorimotor cortex were made by injection of tungstic acid gel. Following ipsilateral lesions of ventral anterior thalamus or the adjacent inferior thalamic peduncle in these animals there was a highly significant reduction in electrographic seizure frequency and duration compared to prelesion control periods. Interictal activity at the focus was not altered. The frequency and duration of spontaneous clinical seizures in five rhesus monkeys with chronic alumina cream foci in motor strip was continuously monitored in activity chairs. Both seizure frequency and duration decreased in all animals in the 4-week period after ipsilateral ventral anterior thalamic lesions as compared to the 4-week control period. Sham lesions did not have these effects. The thalamic lesions did not discernably alter behavior or neurologic function in these primates. Thus ventral anterior thalamic lesions decrease seizure frequency and duration in both acute and chronic experimental models of focal cortical epilepsy. These findings indicate that pathways originating in or passing through the ventral anterior thalamus play a role in the generalization of focal cortical seizures. These lesions in ventral anterior thalamus may be useful in the treatment of medically intractable seizures secondary to foci inaccessible to direct excision.     

Effects of hippocampal lesions on spatial delayed responses in dog

Thirteen dogs were trained to perform spatial delayed responses to auditory cues in a three-choice Nencki testing apparatus with a delay of 0 s and then 10 s with a criterion of 90% correct responses in 90 consecutive trials. Then six dogs received bilateral surgical removal of the hippocampus via the cortex of the suprasylvian gyrus (without additional injury to the entorhinal and parahippocampal cortex). Three dogs received control surgical ablation of the suprasylvian gyrus, which was damaged in ablation of the hippocampus, and four dogs served as intact controls. After the surgery or rest period, the dogs were tested for their retention (10-s delay), and then they were given additional tests with extended delays (30, 60, and 120 s) and with distractions during the 60-s delay period. In comparison with both control groups, dogs with hippocampal ablations had moderately impaired postoperative retention, as evidenced by the elevated numbers of errors on criterion. In subsequent stages of testing with extended delays, the impairment was greater and was significantly correlated with the extent of injury to the hippocampus. These data, together with an analysis of the animals' responses to the three-choice situation, indicate that in dogs lesions of the hippocampus impair spatial memory. © 1995 Wiley-Liss, Inc.     

Effects of medial and dorsal cortex lesions on spatial memory in lizards

In mammals and birds, the hippocampus is a major learning and memory center that plays a prominent role in spatial memory, the use of distal cues to guide navigation. The role of reptilian hippocampal homologues, the medial and dorsal cortex, in spatial memory has not been thoroughly investigated. The medial and dorsal cortex of reptiles is known to play a role in learning both tasks that are hippocampally dependent and tasks that are not hippocampally dependent in mammals and birds. In order to examine the specific role of the medial and dorsal cortex in spatial memory, we trained medial cortex, dorsal cortex, and sham lesioned Cnemidophorus inornatus lizards to locate the one heated rock of four identical rocks spaced evenly around the perimeter of a circular, sand filled, arena in a cool room. We used probe trials to examine the strategies used by lizards to locate the goal. Medial cortex lesions and dorsal cortex lesions slowed acquisition and altered the strategies used to locate the goal. However, none of the lizards adopted a spatial strategy to locate the goal suggesting that the dorsal cortex and medial cortex are involved in using non-spatial strategies for navigation.     

Respiratory rhythmicity after extensive lesions of the dorsal and ventral respiratory groups in the decerebrate cat

It was previously demonstrated that extensive destruction of the regions of the dorsal (DRG) and rostral portions of the ventral respiratory groups (VRG) in the medulla does not disrupt respiratory rhythmicity in the anesthetized cat. The present experiments examined if either higher CNS structures or the caudal expiratory VRG might have been responsible for preserving rhythm in those studies. Results indicate that the DRG and VRG are not required for respiratory rhythmicity in the midcollicularly decerebrated cat.     

Effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on visual discrimination acquisition, performance and reversal in the rat

Rats received infusions of ibotenic acid into the substantia innominata, in the region of the nucleus basalis of Meynert (nbM), before and after training on simple (simultaneous) and conditional visual discriminations. The ibotenate infusions reduced cortical choline acetyltransferase (ChAT) levels by about 20%, destroyed many ChAT-immunoreactive neurons in the nbM, but also caused the loss of many neurons in the substantia innominata and adjacent areas. These lesions did not impair the acquisition and performance of a simple visual discrimination, but did impair reversal of the discrimination and the performance of a conditional visual discrimination. However, the degree of impairment was unrelated to the degree of cortical ChAT loss. Ibotenic acid lesions to the dorsal globus pallidus also impaired reversal of discrimination but left acquisition and performance unaffected. Striatal dopamine depletion produced by 6-hydroxydopamine (6-OHDA) infusions into the mid-ventral caudate nucleus impaired performance of the simultaneous visual discrimination. Cortical noradrenaline depletion produced by 6-OHDA lesions of the dorsal noradrenergic bundle either alone or in combination with ibotenic acid lesions of the substantia innominata had no effect on acquisition of the discrimination. It is concluded that ibotenic acid lesions of the substantia innominata or to the dorsal globus pallidus affect learning and performance of conditional visual discrimination performance and impair reversal learning without affecting the capacity to discriminate visual events. These results are compared to those following cortical noradrenaline depletion or striatal dopamine loss.     

Effects of chemicals on delayed matching behavior in pigeons. III. Effects of triethyltin

The effects of triethyltin (TET) on delayed matching-to-sample performance were studied in male White Carneaux pigeons. Pigeons were trained to peck a red or green center key 15 times to turn it off. After a 2- or 5-sec delay, one side key was illuminated by a red color and the other by a green color. One peck on the side key whose color matched the color that the center key had been, produced food. After performance had stabilized, TET was administered intramuscularly at 3 different dosages (1.75, 3.0 and 5.6 mg/kg) to 3 different groups of birds. Birds received 4 injections of the same dose 2 weeks apart. Responding was totally suppressed in all animals 3 hours after each TET administration at all dosage levels. At 27 and 51 hrs after TET administration, dose-dependent decreases in both matching accuracy and rate of responding were observed. These behavioral changes disappeared in 2 to 3 days.