Rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis (NBM) and sham-operated rats were trained in either a simple discrimination paradigm assessing simple association learning or a negative patterning paradigm assessing configural association learning. In the simple discrimination task, rats were reinforced for responding to a light but were not reinforced for responding to a tone. In the negative patterning discrimination task, rats were reinforced for responding to either a light or a tone presented alone but were not reinforced for responding to both stimuli presented simultaneously. Simple discrimination learning was not affected, whereas acquisition of negative patterning was impaired by NBM lesions. Impaired configural association learning may reflect a loss in the ability of rats with NBM lesions to attend to multiple sensory stimuli or to cope with conflicting response strategies.
Unilateral temporal lobectomy to treat seizure disorders in humans often results in cognitive impairment after the surgery. To determine the potential utility of a rodent model of unilaterally induced cognitive deficits, the present experiment evaluated spatial cognition in adult rats after either left or right hemisphere lesioning of temporal neocortex and underlying hippocampal regions. Evaluation of performance in the eight arm radial maze revealed that both lesioned groups committed more reference memory errors than did nonoperated controls. Working memory errors did not differ statistically between groups. The production of a spatial learning deficit by unilateral damage suggests that this rodent model could serve to test potential improvements in interventional strategies aimed at attenuating cognitive effects of the surgical treatment.
Pathological changes in the hippocampal formation have been noted in schizophrenic patients and manipulation of neurochemical functions within the limbic system has been shown to yield behavioral changes consistent with schizophrenia. The present study evaluated the impact of kainic acid induced hippocampal cellular damage and manipulation of NMDA receptor function (agonism and antagonism) on common behavioral markers of schizophrenia (habituation and prepulse inhibition of the acoustic startle response in rats). Cellular damage significantly impaired habituation and NMDA antagonism disrupted prepulse inhibition. Damage induced impairment of habituation is consistent with effects on latent inhibition (which is also unaffected by NMDA antagonism) while the antagonist disruption of prepulse inhibition is consistent with effects on associative plasticity. The current findings provide further support for a diverse neurobiological substrate of schizophrenic symptoms suggesting that pharmacologic intervention may need to be multifaceted and could involve competing mechanisms. Cognitive impairments may reflect diminished NMDA receptor function whereas positive symptoms may reflect heightened engagement of anatomically disturbed cellular elements.
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