Lesions of the fornix and anterior thalamic nuclei dissociate different aspects of hippocampal-dependent spatial learning: Implications for the neural basis of scene learning.

The present study used 2 different discrimination tasks designed to isolate distinct components of visuospatial learning: structural learning and geometric learning. Structural learning refers to the ability to learn the precise combination of stimulus identity with stimulus location. Rats with anterior thalamic lesions and fornix lesions were unimpaired on a configural learning task in which the rats learned 3 concurrent mirror-image discriminations (structural learning). Indeed, both lesions led to facilitated learning. In contrast, anterior thalamic lesions impaired the geometric discrimination (e.g., swim to the corner with the short wall to the right of the long wall). Finally, both the fornix and anterior thalamic lesions severely impaired T-maze alternation, a task that taxes an array of spatial strategies including allocentric learning. This pattern of dissociations and double dissociations highlights how distinct classes of spatial learning rely on different systems, even though they may converge on the hippocampus. Consequently, the findings suggest that structural learning is heavily dependent on cortico-hippocampal interactions. In contrast, subcortical inputs (such as those from the anterior thalamus) contribute to geometric learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial geniculate lesions block amygdalar and cingulothalamic learning-related neuronal activity

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)+] to avoid a foot shock, and they learn to ignore a different tone (CS-) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CS+ than to the CS-. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas.     

Cue-dependent behavior of hippocampally damaged rats in a complex maze.

In Exp. I, rats with hippocampal lesions were severely impaired in learning a fixed response sequence in a complex maze. Following subsequent manipulations, it was found that hippocampally damaged rats could learn the sequence as well as cortical and operated control Ss in the presence of highly conspicuous cues. Performance of hippocampally damaged Ss, unlike that of the control groups, deteriorated following removal of the cue used in original learning. In Exp. V, Ss with medial thalamic lesions also exhibited maze-learning impairment, but they benefited less than the hippocampal groups from an enhancement of cue conditions. The hippocampus is discussed in terms of its importance in processing relevant stimulus cues and in the organization of appropriate response strategies. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility

The present study examined the performance of rats with neurotoxic lesions centred in the thalamic nucleus medialis dorsalis on standard and modified versions of the eight arm radial maze test. In Experiment 1, the thalamic lesions produced a borderline deficit in acquisition of the standard task, but subsequently had no effect when a delay was interposed after the first four arms had been entered. The same lesions had no effect on T-maze alternation, but they did impair radial-arm maze performance when intramaze and extramaze cues were set against each other. In Experiment 2, lesions of the dorsomedial thalamus impaired acquisition of the standard radial-arm maze task, but combining the results from Experiments 1 and 2 showed that this acquisition deficit was confined to those animals in which bilateral damage extended into the adjacent anterior thalamic nuclei. In addition, lesions of the dorsomedial thalamus disrupted radial-arm maze performance when the task was modified to compare working memory and reference memory and increased activity and exploration. These changes were not associated with anterior thalamic damage. Finally, the thalamic lesions did not affect performance on a test of spontaneous object recognition. It is concluded that lesions of medialis dorsalis do not disrupt spatial memory but do affect other processes that can interact with task performance. These include a failure of extramaze cues to overshadow intramaze cues, a change in activity and exploration levels and deficits in with-holding spatial responses.     

Apparatus Exposure Produces Profound Declines in Conditioned Nictitating-Membrane Responses to Discrete Conditioned Stimuli by the Rabbit (Oryctolagus cuniculus).

The present experiments demonstrated that in the rabbit (Oryctolagus cuniculus) nictitacing-membrane (NM) preparation, exposure to the experimental apparatus produces profound declines in conditioned responding to a discrete conditioned stimulus (CS; Experiments 1, 2A, and 3). Moreover, this decremental effect is at most attenuated in only a minor way when the unconditioned stimulus (US) is presented during exposure to the apparatus (Experiment 2B). Controls for retention loss (Experiments 1 and 3) and for handling and placement in a different context (Experiment 3) did not produce significant declines in responding. These findings challenge theories of extinction that rely primarily on context-US associations but are more consistent with theories that assume context-CS-US associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous Recovery From Forward and Backward Blocking.

This article demonstrates and analyzes spontaneous recovery of stimulus control following both forward and backward blocking in a conditioned suppression preparation with rats. Experiment 1 found, in first-order conditioning, robust forward blocking and an attenuation of it following a retention interval. Experiment 2 showed, in sensory preconditioning, recovery of responding following both forward and backward blocking. Also, the results of this experiment indicated that response recovery to the blocked stimulus cannot be explained by an impaired status of the blocking stimulus after a retention interval. Experiment 3, also in sensory preconditioning, suggested that spontaneous recovery following both forward and backward blocking in Experiment 2 was due to impaired associative activation of the blocking stimulus' representation during testing with the blocked stimulus. Although no contemporary model of associative learning can explain these results, a modification of R. R. Miller and L. D. Matzel's (1988) comparator hypothesis is proposed to do so. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different effects on learning ability after injection of the cholinergic immunotoxin ME20.4IgG-saporin into the diagonal band of Broca, basal nucleus of Meynert, or both in monkeys.

Immunotoxic lesions of the diagonal band of Broca (VDB) in monkeys disrupted cholinergic input to the hippocampus, producing impaired learning of visuospatial conditional discriminations but not simple visual discriminations. Immunotoxic lesions of the basal nucleus of Meynert (NBM) deprived the cortex of most of its cholinergic input, producing impaired learning of simple visual discriminations but not visuospatial conditional discriminations. Combined lesions of the NBM?+?VDB resulted in impaired learning of both types of task. The impairment after NBM lesions ameliorated with time but could be reinstated by a low dose of the glutamate blocking drug MK801, which, at this dose, did not impair simple visual discrimination learning in normal monkeys. The cholinergic projections from the NBM and VDB may sustain the function of the glutamatergic pyramidal cell pathways within the cortex and hippocampus, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visual attention in the rat: A role for the prelimbic cortex and thalamic nuclei?

The behavioral effects of lesions of the prelimbic cortex (PL), mediodorsal nucleus of the thalamus (MD), and anterior thalamic nuclei (ANT) were investigated in 2 attentional tasks in rats: the 5-choice serial reaction time task and a vigilance task. Although there was no lesion effect on accuracy in the 5-choice task, PL lesions enhanced perseverative responding during baseline performance and when stimulus duration was reduced. In contrast, MD lesions increased premature responding during baseline performance and when the intertrial interval was varied unpredictably, In the vigilance paradigm, PL lesions also impaired rats' ability to detect the light signal at baseline and at the reduced stimulus duration. ANT lesions did not substantially disrupt performance. The results suggest that different aspects of attention may be attributable to the PL and the MD and that the mechanisms underlying inhibitory control of behavior may be attributable to functionally different thalamocortical circuits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the retrosplenial cortex in processing multiple conditioned stimuli.

Lesions of retrosplenial cortex (RSP) disrupt spatial and contextual learning, suggesting that RSP may have a fundamental role in processing overlapping, or simultaneously presented stimuli. If so, then RSP lesions might also be expected to disrupt learning that requires the concurrent processing of phasic conditioned stimuli. In Experiment 1, rats were trained in a compound feature negative discrimination task in which a tone was presented and immediately followed by food on some trials, while on other trials a visual stimulus was simultaneously presented along with the tone and not reinforced. Normal rats learned to discriminate between the trials but RSP-lesioned rats exhibited low levels of conditioning on both types of trials. Experiment 2 demonstrated that this effect was not simply due to a general inability to form associations, since RSP-lesioned rats exhibited normal responding when the visual stimulus was presented alone and paired with food. These findings support the view that RSP has an important role in learning that involves the processing of simultaneously presented stimuli and have implications for understanding the functional relationship between the hippocampus and RSP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of Specific and Nonspecific Thalamic Nuclei Affect Prefrontal Cortex-Dependent Aspects of Spatial Working Memory.

Three studies compared lesions of specific mediodorsal (MD) and nonspecific midline/intralaminar (M/IL) and ventromedial (VM) thalamic nuclei placed to spare the anterior nuclei. Lesions of MD, M/IL, or VM impaired delayed matching trained with retractable levers, a measure of spatial memory affected by prefrontal cortical lesions. The effects of the MD lesion increased at longer retention intervals and thus appeared delay dependent. The effects of M/IL and VM lesions were delay independent. Even when combined, these lesions had no effect on varying choice radial maze delayed nonmatching, a task sensitive to hippocampal or anterior thalamic (but not prefrontal) lesions. These results demonstrate effects of MD, M/IL, and VM lesions distinct from the contributions of hippocampus or anterior thalamus to spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning in rats with caudate-putamen lesions: Unimpaired classical conditioning and beneficial effects of redundant stimulus cues on instrumental and spatial learning deficits.

The effects of caudate-putamen lesions in the rat on conditioning were investigated in 3 experiments. In Exp I, rats with lesions were impaired on a spatial task that required learning to make the correct position response, but no deficit was obtained when the alternatives were differentiated by salient visual cues. Performance remained good even when the visual cues were removed. A classical conditioned suppression paradigm was used in Exp II, and caudate-putamen lesions were found not to impair acquisition of suppression or overshadowing. In Exp III poor instrumental learning in subjects with lesions as retarded acquisition of lever-press responding and depressed variable interval response rates were found. When a light stimulus was present together with reinforced responses, response rates were depressed in the control group (which suggested an overshadowing phenomenon) but were potentiated in the group with lesions. Results show that caudate-putamen lesions did not produce a general deficit in association formation. There was disruption of learning about responses but not stimuli and, moreover, it was found that redundant stimulus cues aided response learning. It appears that for normal subjects, the salience or associability of the response cues may largely-determine the influence of stimuli presented during instrumental conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute alcohol intoxication disrupts brightness but not olfactory conditioning in preweanling rats.

The present experiments tested the effect of acute alcohol administration on Pavlovian conditioning of 21-day-old rats using conditioned stimuli of two different sensory modalities—olfaction, an early developing sensory capacity functional at birth, and vision, a later developing sensory system not becoming functional until approximately 15 days of age. Conditioning and testing were conducted between 30 and 60 min following gastric intubation with either physiological saline or a mildly intoxicating alcohol dose (1.5 g/kg body weight). Brain alcohol levels were observed to remain at a peak and stable concentration during this period (Experiment 1). Alcohol impaired acquisition or expression of conditioned aversions to a visual cue paired with footshock when presented either as a single-element conditioned stimulus or as part of an odor/visual compound stimulus (Experiment 2), but it had no discernible effect on conditioned aversions to an olfactory stimulus that had similarly been paired with footshock (Experiments 2 and 3). The results suggest that alcohol may impair some aspects of learning but spare others, depending perhaps on the particular sensory modality to be conditioned. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an impaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS + significantly less often than controls, failing to discriminate between the CS + and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired processing of local geometric features during navigation in a water maze following hippocampal lesions in rats.

Hippocampal damage impairs navigation with respect to information provided by the shape of an arena. Recent evidence has suggested that normal rats use local geometric information, as opposed to a global geometric representation, to navigate to a correct corner. One implication of this pattern of results is that hippocampal lesions may impair processing of 1 or more of the local geometric features of an environment. The authors therefore investigated the effects of hippocampal cell loss in rats on navigation to a hidden goal with respect to a variety of local cues in an environment with a distinctive shape. Rats with lesions of the hippocampus were impaired in discriminating a right-angled corner from its mirror image. However, they were able to use cues provided by an acute-angled corner (Experiment 1) or a local polarizing cue (Experiment 2). In contrast, lesioned rats were impaired in discriminating long versus short walls (Experiment 3). Results indicate that the hippocampus plays a role in disambiguating locations by processing (metric) information related to the distance between corners. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery of associative function following early amygdala lesions in rats.

Adult rats with amygdala lesions made at either Postnatal Day (PND) 10 or PND40 were tested on a series of reversal tasks that tap the ability to form stimulus–reward associations. PND40 rats were significantly impaired relative to both controls and PND10 rats on learning rate of the original discrimination and subsequent reversals. Analyses of discrete learning phases revealed that the impairment was specific to the postchance phase. The PND10 group was not impaired relative to controls on any measure. These results confirm prior findings that amygdala lesions sustained in adulthood impair the formation of stimulus–reward associations. They also demonstrate that substantial sparing or recovery of function is possible when the lesion is made during early development. Furthermore, the findings support the view that behavioral recovery may be more likely if the lesion is sustained near the time of peak synaptogenesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ibotenic acid lesions of the basolateral, but not the central, amygdala interfere with conditioned taste aversion: Evidence from a combined behavioral and anatomical tract-tracing investigation.

Rats (Rattus norvegicus) with almost complete ibotenic acid lesions (at least 90%) of the basolateral amygdaloid complex (BLA) failed to learn a conditioned taste aversion (CTA; Experiment 1A). In these same BLA rats, the bidirectional parabrachial–insular pathway that courses through the central nucleus of the amygdala (Ce) was shown to be spared (Experiment 1B), indicating that the BLA per se is critical for CTA learning. In contrast to the deleterious effect of BLA lesions on CTA, ibotenic acid lesions of the Ce did not block CTA learning (Experiment 2). Nonreinforced preexposure to the gustatory stimulus attenuated CTA acquisition in normal rats, and, under these conditions, rats with BLA lesions were no longer impaired (Experiment 3). Thus, ibotenic acid lesions centered over the Ce, sparing a considerable extent of the BLA, together with the testing procedure used in previous experiments (e.g., L. T. Dunn & B. J. Everitt, 1988), led to the belief that the CTA deficits reported after electrolytic lesions of the amygdala were the result of incidental damage to fibers of passage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The olfactory thalamocortical system and odor reversal learning examined using an asymmetrical lesion paradigm in rats.

The olfactory thalamocortical system was disrupted bilaterally in rats using (a) unilateral mediodorsal thalamic (MD) lesions plus contralateral bulbectomy and transection of the anterior commissure (AC), (b) unilateral MD lesions plus contralateral lesions of the frontal cortex, or (c) bilateral MD lesions. Rats were trained on an odor discrimination task and on the reversal of that task. Experimental groups performed as well as controls on the initial discrimination tasks but made more errors on the reversal problem. Rats with asymmetrical disruption of the olfactory thalamocortical system performed as poorly as those with bilateral MD lesions. These outcomes indicate that odor reversal learning deficits in rats with bilateral MD lesions stem from interruption of the olfactory thalamic-neocortical system and also provide evidence that the AC mediates significant interhemispheric transfer of olfactory information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsal hippocampal lesions impair blocking but not latent inhibition of taste aversion learning in rats.

The aim of the present experiments was to study the effect of nonselective electrolytic lesions of the rat dorsal hippocampus on 2 learning phenomena: the L. J. Kamin (1969) blocking effect and latent inhibition of taste aversion learning. Bilateral dorsal hippocampal lesions selectively impaired blocking induced by 1 saccharin-lithium chloride pairing previous to 1 serial compound (saccharin–cider vinegar)–lithium pairing, but lesions had no effect on latent inhibition of a saline aversion, induced by 6 saline preexposures, in the same group of animals. Moreover, dorsal hippocampal lesions did not affect latent inhibition of saccharin-conditioned aversion induced by 1 or 6 preexposures. It is argued that blocking and latent inhibition of taste aversion learning do not share a common neural mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal modulation of cingulo-thalamic neuronal activity and discriminative avoidance learning in rabbits

Two experiments assessed the effects of 1) combined subicular complex and posterior cingulate cortical lesions on training-induced neuronal activity (TIA) in the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei; 2) hippocampal (Ammon's horn and dentate gyrus) lesions on TIA in cingulate cortex and in the AV and MD thalamic nuclei. The rabbits acquired a conditioned avoidance response (CR), stepping in an activity wheel upon hearing a 0.5-s tone (CS+), in order to prevent a foot-shock scheduled 5 s after tone onset. No response was required after a different, safety-predictive tone (CS-). In experiment 1 the combined subicular and cingulate cortical lesions enhanced thalamic TIA during acquisition and increased CR incidence in the first session of acquisition. These results confirmed the hypothesis that subicular and cingulate cortical efferents are not essential for thalamic TIA or for avoidance learning. Hippocampal lesions (experiment 2) also enhanced thalamic TIA. However, unlike subicular lesions, hippocampal lesions enhanced posterior cingulate cortical TIA as well, especially during extinction training. Hippocampal lesions did not affect CR performance. The results suggested that subicular excitatory efferents are responsible for incrementing cingulate cortical TIA, which is viewed as subserving associative attention. Activity from hippocampus downregulates the cue-elicited neuronal activity of the cingulo-thalamic circuits by suppressing the excitatory influence of the subiculum. The hippocampal influence reduces cingulo-thalamic cue-elicited activation in particular circumstances, such as the onset of CR extinction, when an expected reinforcer is omitted.     

Contributions of postrhinal and perirhinal cortex to contextual information processing.

The role of the postrhinal cortex (POR) and the perirhinal cortex (PER) in processing relational or contextual information was examined with Pavlovian fear conditioning. Rats with electrolytic or neurotoxic lesions of the POR or PER were tested in 2 contextual fear conditioning paradigms. In Experiment 1, electrolytic lesions of the POR or PER produced impairments in contextual fear conditioning but not in conditioning to a phasic auditory conditioned stimulus. Neurotoxic lesions of the POR or PER likewise resulted in anterograde (Experiment 2) and retrograde (Experiment 3) deficits in fear conditioning to the training context in an unsignaled shock paradigm. The results suggest that operations performed on sensory information by the POR and PER are necessary to support contextual learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)