RESUMEN
The hippocampus is critical for spatial memory. Recently, subregional differences in the function of hippocampus have been described in a number of behavioral tasks. The present experiments assessed the effects of reversibly lesioning either the dorsal (dHip) or ventral hippocampus (vHip) on spontaneous tests of spatial recognition and temporal order memory. We report that although the dHip is necessary for spatial recognition memory (RM) (distinguishing a novel from a familiar spatial location), the vHip is involved in temporal order memory (the capacity to distinguish between two spatial locations visited at different points in time), but not RM. These findings and others are consistent with the hypothesis that temporal order memory is supported by an integrated circuit of limbic areas including the vHip and the medial prefrontal cortex.
Asunto(s)
Hipocampo/fisiología , Trastornos de la Memoria/fisiopatología , Memoria/fisiología , Reconocimiento en Psicología/fisiología , Percepción Espacial/fisiología , Percepción del Tiempo/fisiología , Animales , Desnervación , Hipocampo/anatomía & histología , Sistema Límbico/anatomía & histología , Sistema Límbico/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Corteza Prefrontal/anatomía & histología , Corteza Prefrontal/fisiología , Ratas , Ratas Long-EvansRESUMEN
The neural mechanisms mediating prepulse inhibition (PPI) appear to have relevance to neurological and psychiatric disorders. Patients with temporal lobe epilepsy exhibit psychotic symptoms and disrupted PPI, therefore the present experiments examined the consequences of seizures induced by kindling on PPI. Rats were chronically implanted with an electrode into the basolateral amygdala, perirhinal cortex, or ventral hippocampus and stimulated twice daily until 3 fully generalized, class 5 seizures were elicited. Kindling of basolateral amygdala, but not perirhinal cortex or ventral hippocampus, disrupted PPI when testing began 2min, but not 48h, following the elicitation of the third class 5 seizure. Startle amplitudes were unaffected by kindling. These results suggest that the anatomical origin of seizures is an important factor in determining their potentially disruptive effects on PPI.
Asunto(s)
Amígdala del Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Trastornos Neurológicos de la Marcha/fisiopatología , Hipocampo/fisiopatología , Excitación Neurológica/fisiología , Análisis de Varianza , Animales , Conducta Animal , Modelos Animales de Enfermedad , Trastornos Neurológicos de la Marcha/patología , Inhibición Psicológica , Masculino , Ratas , Ratas Long-Evans , Reflejo de Sobresalto/fisiologíaRESUMEN
Abnormal activity in corticolimbic circuits during development may be a predisposing factor for schizophrenia. Permanent or temporary lesions of limbic structures such as the ventral hippocampus and basolateral amygdala in rats on postnatal day (PND) 7 result in functional changes similar to some behavioural and cognitive signs of schizophrenia. The present experiments tested whether transient increases in the neural activity of corticolimbic circuits on PND 7 would result in similar behavioural changes. Long-Evans rats were treated with either kainic acid (KA, 1.5 mg/kg, i.p.) or saline on PND 7 and tested for prepulse inhibition (PPI) of the acoustic startle response and spontaneous locomotor activity both in a novel environment and following amphetamine treatment before puberty (PND 35) and in early adulthood (PND 56). In subgroups of animals PPI was also measured following apomorphine administration (0.2 mg/kg) and spatial learning and memory were tested in the water maze. Rats treated with KA were indistinguishable from saline-treated animals on PND 35. However, on PND 56, KA-treated animals showed a subtle consistent decrease in PPI relative to control animals, but did not show increased sensitivity to the disruptive effects of a low dose of apomorphine on PPI. Locomotor responses to novelty or amphetamine were not reliably altered in the KA-treated animals. KA- and saline-treated animals performed similarly in the water maze. These results support the hypothesis that neural hyperactivity on PND 7 in rats causes behavioural changes in early adulthood that resemble some symptoms of schizophrenia. These pharmacological data suggest that the changes are not mediated by postsynaptic alterations in mesolimbic dopamine transmission.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Inhibición Psicológica , Ácido Kaínico/toxicidad , Sistema Límbico/efectos de los fármacos , Esquizofrenia/inducido químicamente , Estimulación Acústica/métodos , Factores de Edad , Anfetamina/farmacología , Animales , Animales Recién Nacidos , Apomorfina/farmacología , Conducta Animal , Corteza Cerebral/fisiología , Modelos Animales de Enfermedad , Agonistas de Dopamina/farmacología , Inhibidores de Captación de Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Agonistas de Aminoácidos Excitadores/toxicidad , Conducta Exploratoria/efectos de los fármacos , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/patología , Sistema Límbico/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Embarazo , Ratas , Ratas Long-Evans , Tiempo de Reacción/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Esquizofrenia/fisiopatologíaRESUMEN
The present study investigated the roles of the perirhinal cortex, medial prefrontal cortex, and intrahemispheric interactions between them in recognition and temporal order memory for objects. Experiment 1 assessed the effects of bilateral microinfusions of the sodium channel blocker lidocaine into either the anterior perirhinal or medial prefrontal cortex immediately before memory testing in a familiarity discrimination task and a recency discrimination task, both of which involved spontaneous exploration of objects. Inactivation of the perirhinal cortex disrupted performance in both tasks, whereas inactivation of the medial prefrontal cortex disrupted performance in the recency, but not the familiarity, discrimination task. In a second experiment, the importance of intrahemispheric interactions between these structures in temporal order memory were assessed by comparing the effects of unilateral inactivation of either structure alone with those of crossed unilateral inactivation of both structures on the recency discrimination task. Crossed unilateral inactivation of both structures produced a significant impairment, whereas inactivation of either structure alone produced little or no impairment. Collectively, these findings suggest that the perirhinal cortex, but not the medial prefrontal cortex, contributes to retrieval of information necessary for long-term object recognition, whereas both structures, via intrahemispheric interactions between them, contribute to retrieval of information necessary for long-term object temporal order memory. These data are consistent with models in which attributed information is stored in posterior cortical sites and supports lower-order mnemonic functions (e.g., recognition memory) but can also be retrieved and further processed via interactions with the prefrontal cortex to support higher-order mnemonic functions (e.g., temporal order memory).
Asunto(s)
Memoria/fisiología , Giro Parahipocampal/fisiología , Corteza Prefrontal/fisiología , Reconocimiento en Psicología/fisiología , Animales , Discriminación en Psicología/efectos de los fármacos , Discriminación en Psicología/fisiología , Vías de Administración de Medicamentos , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Memoria/efectos de los fármacos , Vías Nerviosas/fisiología , Giro Parahipocampal/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Ratas , Ratas Long-Evans , Reconocimiento en Psicología/efectos de los fármacos , Bloqueadores de los Canales de Sodio/farmacología , Factores de TiempoRESUMEN
Temporal lobe epilepsy, the most common type of epilepsy in adult humans, is characterized clinically by the progressive development of spontaneous recurrent seizures of temporal lobe origin and pathologically by hippocampal neuronal loss and mossy fiber sprouting. In this study, we sought to test the prominent hypothesis that neuronal loss and mossy fiber sprouting play a critical role in the genesis and progression of temporal lobe epilepsy. Rats receiving a single kainic acid injection experienced a single sustained episode of epileptic status with massive neuronal loss and mossy fiber sprouting, whereas rats receiving triple kainic acid injections experienced two priming episodes and one sustained episode of epileptic status with no detectable neuronal loss and mossy fiber sprouting. Early in the process of chronic seizure development, primed rats that failed to show detectable neuronal loss and mossy fiber sprouting exhibited a starting date and a frequency of spontaneous recurrent seizures similar to those of nonprimed rats that showed massive neuronal loss and mossy fiber sprouting. However, nonprimed rats displayed significantly prolonged episodes of spontaneous recurrent seizures over the whole process of chronic seizure development and more frequent severe seizures later in the process. Similar results were observed in both Fischer-344 and Wistar rats as well as in the rat pilocarpine preparation of temporal lobe epilepsy. These results fail to reveal a relation between neuronal loss-mossy fiber sprouting and the genesis of temporal lobe epilepsy but suggest that neuronal loss, mossy fiber sprouting, or both contribute to the intensification of chronic seizures.