Selective fimbria and thalamic lesions differentially impair forms of working memory in rats

doi:10.1016/0163-1047(91)90364-V

Behavioral and Neural Biology

Volume 56, Issue 3, November 1991, Pages 221-239

https://doi.org/10.1016/0163-1047(91)90364-V Get rights and content

Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes.

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Rodent studies have typically employed spatially guided delayed-response tasks, in which the animal is required to retain a memory trace of a recently sampled maze location during a delay period and is then prompted to select the opposite location to receive a reward (delayed nonmatching-to-sample [DNMS] task). Many studies have reported deficits after lesions or inhibition of the MD using variants of the DNMS task (33–41). Although in some of these studies lesions may have extended to adjacent regions, including the anterior thalamus (33–35), the MD, unlike the anterior thalamus, does not seem to play a role in spatial-reference memory (42).
Deficits in cognition are a core feature of many psychiatric conditions, including schizophrenia, where the severity of such deficits is a strong predictor of long-term outcome. Impairment in cognitive domains such as working memory and behavioral flexibility has typically been associated with prefrontal cortex (PFC) dysfunction. However, there is increasing evidence that the PFC cannot be dissociated from its main thalamic counterpart, the mediodorsal thalamus (MD). Since the causal relationships between MD-PFC abnormalities and cognitive impairment, as well as the neuronal mechanisms underlying them, are difficult to address in humans, animal models have been employed for mechanistic insight. In this review, we discuss anatomical, behavioral, and electrophysiological findings from animal studies that provide a new understanding on how MD-PFC circuits support higher-order cognitive function. We argue that the MD may be required for amplifying and sustaining cortical representations under different behavioral conditions. These findings advance a new framework for the broader involvement of distributed thalamo-frontal circuits in cognition and point to the MD as a potential therapeutic target for improving cognitive deficits in schizophrenia and other disorders.
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Both spatial and non-spatial tests of working memory have been extensively applied to rodents with MD lesions, without providing conclusive evidence for a specific involvement of MD in this function. As mentioned above, several examples of deficits in spatial working memory tasks could have resulted from the effect of unwanted damage to other thalamic nuclei (Burk and Mair, 1998; M’Harzi et al., 1991; Stokes and Best, 1990a,b; Young et al., 1996). In a number of cases, MD lesions had little or no effect in the standard radial-arm maze task (Alexinsky, 2001; M’Harzi et al., 1991) or on spatial reinforced alternation in a cross-maze.
Today, the idea that the integrity of the limbic thalamus is necessary for normal memory functions is well established. However, if the study of thalamic patients emphasized the anterior and the mediodorsal thalamus as the critical thalamic loci supporting cognitive functions, clinical studies have so far failed to attribute a specific role to each of these regions. In view of these difficulties, we review here the experimental data conducted in rodents harboring specific lesions of each thalamic region. These data clearly indicate a major functional dissociation within the limbic thalamus. The anterior thalamus provides critical support for hippocampal functions due to its cardinal location in the Papez circuit, while the mediodorsal thalamus may signal relevant information in a circuit encompassing the basolateral amygdala and the prefrontal cortex. Interestingly, while clinical studies have suggested that diencephalic pathologies may disconnect the medial temporal lobe from the cortex, experimental studies conducted in rodent show how this may differently affect distinct temporo-thalamo-cortical circuits, sharing the same general organization but supporting dissociable functions.
Contribution of the parafascicular nucleus in the spontaneous object recognition task
2011, Neurobiology of Learning and Memory
The parafascicular (PF) nucleus, a posterior component of the intralaminar nuclei of the thalamus, is considered to be an essential structure in the feedback systems of basal ganglia–thalamo-cortical circuits critically involved in cognitive processes. The specific role played by multimodal information encoded in PF neurons in learning and memory processes is still unclear. We conducted two experiments to investigate the role of the PF in the spontaneous object recognition (SOR) task. The behavioral effects of pretraining rats with bilateral lesions of PF with N-methyl-D-aspartate (NMDA) were compared to vehicle controls. In the first experiment, rats were tested on their ability to remember the association immediately after training trials and in the second experiment after a 24 h delay. Our findings provide evidence that PF lesions critically affect both SOR tests and support its role in that non-spatial form of relational memory.
Effects of ethanol on hippocampal function during adolescence: A look at the past and thoughts on the future
2010, Alcohol
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Hippocampal lesions made by any method, before or after training, permanently impair performance in spatial tasks as long as the animal does not learn a stereotyped response pattern (for review, see Shapiro, 2001). Direct lesions to the hippocampus lead to spatial memory deficits (Clark et al., 2005; Eichenbaum et al., 1990); lesions to the fimbria/fornix, the major afferent pathway to the hippocampus, produce impaired place recognition but spare object recognition (M'Harzi et al., 1991) and facilitate nonspatial reference memory (Chang and Gold, 2003; Matthews and Best, 1995; Schroeder et al., 2002). Reversible inactivation of the hippocampus also disrupts early spatial memory processing (Packard and McGaugh, 1996).
It has been demonstrated by several laboratories that ethanol, both acute and chronic, produces effects that are age dependent. Specifically, adolescent rats are less sensitive to the hypnotic and motor-impairing effects of ethanol but are more sensitive to the hypothermic effects of the drug. However, the results on hippocampal function are not as clear. For example, there have been mixed findings regarding adolescent sensitivity of hippocampal-dependent (spatial) memory in response to ethanol. The current review explores the present state of the field as it relates to ethanol's effects in the hippocampus, particularly as it relates to spatial memory. In addition, we review potential neurobiological mechanisms that might underlie the age-dependent effects of ethanol in the hippocampus. Finally, future directions are proposed that will advance the state of the field as it relates to ethanol's effect during this developmental period.
Spared place and object-place learning but limited spatial working memory capacity in rats with selective lesions of the dentate gyrus
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We studied the cognitive performance of rats with colchicine-induced lesions of the hippocampal dentate gyrus (DG) on a range of spatial, non-spatial and mixed spatial/procedural tasks. Rats were assigned to three experimental groups receiving large colchicine lesions (7 μg per hippocampus), small colchicine lesions (1.75 μg per hippocampus) or sham lesions. Stereological estimates of cell density indicated that the colchicine treatments induced dose-dependent damage to the DG, while sparing in large part other hippocampal subfields. Remarkably, the behavioural results showed that the colchicine lesions did not affect the performance of rats in an object discrimination task, in an object-place associative task in which a familiar object was displaced from a given position nor in a spontaneous spatial discrimination task performed in the T-maze. However, rats in both lesion groups were severely impaired in a reinforced non-matching-to-position working memory task conducted in the T-maze. Importantly, performance in the working memory task correlated strongly with cell density in the DG but not with cell density in the CA1 and CA3 areas. Only rats with large-lesions showed a transient deficit in a reinforced rule-based conditional discrimination task. These data demonstrated that rats with selective lesions of the DG readily acquire and retain neural representations relative to objects and places but are specifically impaired in their ability to update rapidly and flexibly spatial information that is essential to guide goal-directed actions.
Excitotoxic lesions of the parafascicular nucleus produce deficits in a socially transmitted food preference
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The parafascicular (PF) nucleus, a posterior component of the intralaminar nuclei of the thalamus, is considered to be an essential structure in the feedback circuits of basal ganglia-thalamo-cortical systems that critically participate in cognitive processes. To study the PF contribution to processing of behaviorally significant information during specific episodes of learning, we investigated the effects of damaging the PF nucleus in the acquisition of a natural form of social olfactory learning, the socially transmitted food preference (STFP) task. This task is a non-spatial paradigm that exhibits some of the characteristics of relational memory because it requires that animals use information obtained in one episode to guide later behavior in different circumstances. Adult male Wistar rats were submitted to pretraining bilateral N-methyl-d-aspartate (0.15 M, pH 7.4) lesions of the PF (0.4 μl/side, 0.2 μl/min). The behavioral effects of PF lesions were compared to vehicle- and sham-operated control groups and two retention delays were considered in separate groups: immediately (Lesion-I, Vehicle-I, and Sham-I groups) and 24 h after training (Lesion-24, Vehicle-24, and Sham-24 groups). PF lesions produced delay-independent impairments in the STFP suggesting that this nucleus might modulate the acquisition of this odor–odor association task. Results are discussed in the context of medial prefrontal cortex deafferentation induced by PF damage.

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¹: This research was supported by a grant (88/178) from DRET.

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Selective fimbria and thalamic lesions differentially impair forms of working memory in rats1

Behavioural Brain Research

Neuropsychologia

Trends in Neuroscience

Behavioral and Neural Biology

Behavioral Neural Biology

Neuroscience

Brain Research

Behavioural Brain Research

Journal of Neuroscience Methods

Experimental Neurology

Physiology and Behavior

Behavioural Brain Research

Brain Research Reviews

Progress in Neurobiology

Experimental Neurology

Physiology and Behavior

Physiology and Behavior

Physiology and Behavior

Neurobiology of Aging

Behavioural Brain Research

Behavioural Brain Research

Neuropsychologia