Dopamine in the lateral caudate-putamen of the rat is essential for somatosensory orientation.

Two studies examined the possible localization of somatosensory orientation in the caudate putamen (CP) of the rat. In Exp I 6-hydroxydopamine (6-OHDA [6 μg]) was injected into either the anterodorsal (AD), anteroventral (AV), posterodorsal (PD), or posteroventral (PV) CP of 19 Long-Evans and 39 Sprague-Dawley rats. Only Ss with PV-CP 6-OHDA injections showed impaired orientation scores. However, these PV injections often caused widespread CP dopamine (DA) depletions, and no specific CP region appeared to be particularly associated with somatosensory orientation. In Exp II, with 32 male Sprague-Dawley rats, multiple injections of 6-OHDA were directed toward the medial or lateral CP to assess their relative contributions directly. DA depletions confined to the lateral (but not medial) CP resulted in orientation deficits; these deficits were greater than would be predicted from the volume of CP/DA loss. The magnitude of the DA fluorescence loss in the lateral CP was more highly correlated with the orientation impairment than was the medial CP fluorescence loss. Thus, the lateral CP contributes to sensorimotor functions to a greater extent than does the medial CP, but the volume of CP/DA depletion also appears to be important. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective immunotoxic lesions of basal forebrain cholinergic cells: Effects on learning and memory in rats.

Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: Role of cholinergic medial septal neurons in spatial working memory.

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of item and order memory following parietal cortex lesions in the rat.

Rats with parietal cortex lesions were tested for both item and order memory for a list of spatial events in a probe recognition procedure. Rats with parietal cortex lesions were impaired for all events within the item memory task but had good memory for the early events within the order memory task. These data suggest a dissociation of function between item and order memory for parietal cortex damaged animals. In conjunction with previous findings with rats with medial prefrontal cortex lesions, these data suggest that item and order memory can be coded and represented independently. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory deficits in patients with lesions to the right hippocampus and to the right parahippocampal cortex

Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory.     

The effect of catecholaminergic depletion within the prelimbic and infralimbic medial prefrontal cortex on recognition memory for recency, location, and objects.

There is good evidence that the medial prefrontal cortex (mPFC) is involved in different aspects of recognition memory. However, the mPFC is a heterogeneous structure, and the contribution of the prelimbic (PL) and infralimbic (IL) cortices to recognition memory has not been investigated. Similarly, the role of different neuromodulators within the mPFC in these processes is poorly understood. To this end, we tested animals with 6-hydroxydopamine (6-OHDA) lesions of the PL and IL mPFC on three tests of object recognition memory that required judgments about recency, object location, and object identity. In the recency task, lesions to both PL and IL severely impaired animals' ability to differentiate between old (earlier presented) and recently presented familiar objects. Relative to sham and PL animals, the IL lesion also disrupted performance on the object location task. However, both lesions left novel object recognition intact. These data confirm previous reports that the mPFC is not required for discriminations based on the relative familiarity of individual objects. However, these results demonstrate that catecholamines within the PL cortex are crucial for relative recency judgments and suggest a possible role for neural processing within the IL in the integration of information about object location. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Basal forebrain lesions and memory: Alterations in neurotensin, not acetylcholine, may cause amnesia.

Behavioral impairments produced by lesions of the nucleus basalis magnocellularis (NBM) are usually attributed to the loss of cholinergic cells. A comparison between the effects of 2 different neurotoxins, ibotenic (IBO) and quisqualic (QUIS) acid, reveals that this interpretation is inconsistent with the data. Rats were given injections of either IBO or QUIS into the NBM and tested on an alternation task in a T-maze. At the start of behavioral testing, both IBO and QUIS rats had impaired choice accuracy. At the end of behavioral testing, however, IBO rats, but not QUIS rats, were more impaired than controls, and IBO rats were more impaired than QUIS rats. IBO decreased choline acetyltransferase (ChAT) activity and [–3H]neurotensin binding in the neocortex. QUIS decreased ChAT activity but did not change [–3H]neurotensin binding. The cholinergic system may not be the critical component responsible for behavioral impairments following NBM lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term effects of selective neonatal temporal lobe lesions on learning and memory in monkeys.

Rhesus monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal cortical area TE, and their normal controls, were reassessed in visual habit formation (24-hour intertrial interval task) and visual recognition (delayed nonmatching to sample [DNMS]) at 4–5 years of age and then tested on tactile and spatial DNMS. Results on the two visual tasks were the same as those obtained when the monkeys were under 1 year of age. Specifically, early medial temporal lesions, like late lesions, left habit formation intact but severely impaired recognition memory. Furthermore, the memory deficit extended to the tactile and spatial modalities. By contrast, early damage to TE, unlike late damage to it, yielded only mild deficits on both visual tasks and had no effect on tactile or spatial DNMS. Compensatory mechanisms that promote substantial and permanent recovery thus appear to be available after neonatal TE lesions but not after neonatal medial temporal lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Hippocampus and Medial Caudate Nucleus Lesions on Memory for Direction Information in Rats.

A delayed matching-to-sample task was designed to assess memory for direction information in rats. During the study phase, rats traversed a maze arm oriented in 1 of 3 directions. After a delay period, a test phase was presented that required a choice between the study phase direction and a foil direction. Once rats reached a learning criterion, probe trials suggested that normal rats favor the use of direction, rather than turning response, information and use vestibular feedback. Rats were then given hippocampus, medial caudate nucleus (MCN), or cortical control lesions. Unlike control rats, those with hippocampus and MCN lesions exhibited marked impairments when retested. However, all rats were able to learn a direction discrimination task. These results suggest that the hippocampus and MCN support processes associated with short-term memory for direction information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Item and order information in spatial memory.

14 male Holtzman albino rats were taught to perform order and item discriminations in an 8-arm radial maze. In Exp I, 2 groups of Ss learned different order discriminations with reward contingent on repeating or avoiding the most recently visited of 2 locations. Each trial began with a random order of 8 forced choices and ended with a choice between the 1st and 7th arms. Rate of learning depended on the compatibility of reward contingencies and preexperimental response biases. In Exp II, each trial began with a list of 7 forced choices and ended in a choice between either the 1st or 6th arm and the arm not presented; accuracy of performing these item discriminations depended on both serial position and the response tendencies acquired in Exp I. In Exp III, a 1-hr postlist delay impaired the order discrimination more than the item discrimination, and the effects of intertrial interval depended on previously acquired response biases. Results are discussed in terms of a 2-stage model that segregates a single memory process from decision/response processes. Item and order discriminations do not appear to be based on separate sources of information and do not appear to require fundamentally different memory processes. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cholinergic agent physostigmine enhances short-term-memory-based performance in the developing rat.

There are age-related differences in the rat's short-term memory processes. Rats 24–25 days old are 90% correct when the delay interval separating the forced run and choice run of a trial is either 10 or 30 s, but they perform at chance when the delay interval is 60 s. In contrast, the choice performance of 30-day-old rats remains constant across all delay intervals. It is reported that the cholinergic agent physostigmine dramatically improved the short-term-memory-based performance of rats 24–25 days old such that they displayed no loss in choice accuracy even when the delay interval was 60 s. No such enhanced performance was seen in rats treated with neostigmine, a peripherally acting anticholinesterase. The results support the hypothesis that postnatal maturational differences in central cholinergic systems may contribute to age-related differences in short-term memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training.

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition that is invariant over many trials. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term effects of neonatal damage to the hippocampal formation and amygdaloid complex on object discrimination and object recognition in rhesus monkeys (Macaca mulatta).

Rhesus monkeys with neonatal aspiration lesions of the hippocampal formation or the amygdaloid complex were tested on concurrent discrimination learning (24-hr intertrial interval [ITI]) at 3 months, on object recognition memory (delayed nonmatching-to-sample [DNMS]) at 10 months, and retested on both tasks at 6–7 years of age. Neonatal amygdaloid damage mildly impaired acquisition at the 24-hr ITI and the performance test of DNMS at both ages. In contrast, early hippocampal lesions impaired performance only on the longest lists of 10 items in DNMS in adult monkeys. Thus, early amygdala lesions appeared to have resulted in a greater object memory loss than early hippocampal lesions. However, in light of recent findings from lesion studies in adult monkeys, the object memory impairment after early amygdaloid lesions is better accounted for by damage to the entorhinal and perirhinal cortex than by damage to the amygdaloid nuclei. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of rat perirhinal cortex exacerbate the memory deficit observed following damage to the fimbria-fornix.

Rats that had received bilateral lesions of the perirhinal cortex, fimbria-fornix, combined lesions of both these structures, or sham operations were tested on an object-guided delayed non-match-to-sample task. Perirhinal lesioned and fimbria-fornix lesioned rats were moderately impaired when delay intervals of 30 s or more were introduced between the sample and test phases of the experiment. Animals with combined lesions displayed a considerably greater impairment than animals with lesions of either structure alone. The combined lesioned animals were severely impaired in the initial acquisition of the task and displayed a profound memory deficit at delay intervals of greater than 4 s. These results emphasize the importance of the perirhinal cortex to memory function and suggest that the perirhinal cortex and the hippocampal formation may function interactively in the execution of memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of perforant path lesions in rodent models of memory and attention

Early stage Alzheimer's disease (AD) pathology is associated with neurodegeneration of systems within the temporal cortex, e.g. the entorhinal cortex, perforant pathway and hippocampus. The perforant pathway provides the major neuronal input to the hippocampus from the entorhinal cortex and thus relays multimodal sensory information derived from cortical zones into the hippocampus. The earliest symptoms of AD include cognitive impairments, e.g. deficits in short-term memory and attention. Consequently, we have investigated the effect of bilateral knife cut lesions to the perforant path on cognition in rats using models measuring primarily short-term memory (operant delayed match to position task), attention (serial five-choice reaction time task) and spatial learning (Morris water maze). Rats receiving bilateral perforant path lesions showed normal neurological function and a mild hyperactivity. The lesion produced little effect on attention assessed using the five-choice task. In contrast, animals with equivalent lesions showed a robust delay-dependent deficit in the delayed match to position task. Spatial learning in the water maze task was also severely impaired. The delay-dependent deficit in the match to position task was not reversed by tacrine (3 mg/kg) pretreatment. The present data support a selective impairment of cognitive function following perforant path lesions that was confined to mnemonic rather than attentional processing. These findings complement primate and human studies identifying a critical role of the perforant pathway and associated temporal lobe structures in declarative memory. Degeneration of the perforant pathway is likely to contribute to the mnemonic deficits characteristic of early AD. The failure of tacrine to ameliorate these deficits may be relevant to an emerging clinical literature suggesting that cholinomimetic therapies improve attentional rather than mnemonic function in AD.     

Medial auditory thalamic nuclei are necessary for eyeblink conditioning.

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated with induced lesions of the medial auditory thalamus contralateral to the trained eye in rats. Rats were given unilateral lesions of the medial auditory thalamus or a control surgery followed by twenty 100-trial sessions of delay eyeblink conditioning with a tone CS and then five sessions of delay conditioning with a light CS. Rats that had complete lesions of the contralateral medial auditory thalamic nuclei, including the medial division of the medial geniculate, suprageniculate, and posterior intralaminar nucleus, showed a severe deficit in conditioning with the tone CS. Rats with complete lesions also showed no cross-modal facilitation (savings) when switched to the light CS. The medial auditory thalamic nuclei may modulate activity in a short-latency auditory CS pathway or serve as part of a longer latency auditory CS pathway that is necessary for eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal system dysfunction and odor discrimination learning in rats: Impairment of facilitation depending on representational demands.

The performance of normal rats and that of rats with hippocampal system damage were compared on acquisition of different versions of the same two-odor discrimination task that placed different encoding and representational demands on memory. Rats with fornix lesions were impaired when explicit comparisons among multiple odor cues and differential response choices were encouraged. However, when odor-cue comparisons was hindered and explicit cues for response choice were eliminated, rats with fornix lesions out performed normal animals. The results support a hypothesis that the hippocampal system is critical to a memory representation based on encoding relations among multiple percepts, and other brain systems support performance adaptations based on encodings of stimuli individually. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amnestic mild cognitive impairment: Difference of memory profile in subjects who converted or did not convert to Alzheimer's disease.

Episodic long-term, short-term, and implicit memory were investigated in 79 elderly subjects who fulfilled criteria for the amnestic form of mild cognitive impairment (a-MCI; i.e., by having an idiopathic amnestic disorder with absence of impairment in cognitive areas other than memory and without confounding medical or psychiatric conditions) and who developed Alzheimer's disease (AD) after 2 years as well as in 111 subjects affected by a-MCI who did not develop dementia. Results document a memory profile in a-MCI subjects characterized by preserved short-term and implicit memory and extensive impairment of episodic long-term memory. In virtually all episodic memory indexes examined (learning, forgetting, recognition abilities), a-MCI subjects who converted to AD were more severely impaired than were subjects who did not become demented. This memory profile, which closely resembles that exhibited by amnestic patients with bilateral mesial-temporal lobe lesions, confirms a precocious phase in preclinical AD characterized by selective involvement of mesial-temporal areas and worsening of the memory impairment as atrophic changes progress in hippocampal structures. In this context of pervasive episodic memory impairment, tests assessing the free recall of verbal material following a delay interval demonstrated the greater sensitivity to memory deficits of a-MCI subjects who developed AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of the effects of bilateral and unilateral infusions of muscimol into the basal forebrain on cued detection of visual targets in rats.

This study investigated the role of the basal forebrain cholinergic system (BFCS) in rats' performance of a visuospatial attention task. Muscimol was infused bilaterally and unilaterally into the BFCS to inhibit cholinergic projections to the cortex. Muscimol slowed responding without significantly affecting side-bias. Bilateral infusions increased accuracy for all targets, whereas unilateral infusions reduced accuracy for targets contralateral to the infusion and increased accuracy for targets ipsilateral to the infusion. After a low unilateral dose of muscimol, invalid cues impaired detection of contralateral targets and spared detection of ipsilateral targets. A high unilateral dose of muscimol impaired detection of contralateral targets independently of cueing. These results suggest that interhemispheric imbalance in cortical activity by pharmacological manipulation of the BFCS can impair the detection of lateralized visual stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.

The effect of injection into the medial septum of a toxin selective for cholinergic neurons, 192 IgG-saporin, was examined in rats trained to perform 2 versions of the radial 8-arm maze task. Rats were first trained to perform a task with varying delays (0, 1, 2 min) imposed between the 4th correct arm choice and access to all 8 arms. Lesioned rats made significantly more errors in the first 4 choices compared with controls and significantly more errors after delays; however, this effect was not delay dependent. Rats were then trained on a different version of this 8-arm maze task in which they learned to avoid 2 arms that were never baited. There was no treatment effect on acquisition of this task. These data are consistent with the hypothesis that the cholinergic projection to the hippocampus facilitates the acquisition of information into the system responsible for short-term memory for locations visited (spatial working memory) but is not involved in retention of this information. It also appears to play no role in either the acquisition or retention of place-nonreward associations (spatial reference memory). (PsycINFO Database Record (c) 2010 APA, all rights reserved)