Blockade of NMDA receptors in the amygdala prevents latent inhibition of fear-conditioning.

The association between a conditioned stimulus (CS) and an unconditioned stimulus (US) in fear-conditioning depends on N-methyl-D-aspartate (NMDA) receptors in the basolateral amygdala complex (BLA). Latent inhibition (LI) is the retardation in learning due to nonreinforced presentation of the prospective CS before conditioning. Disruption of LI in rats is an animal model of schizophrenia, reflecting the deficits of schizophrenic patients in neglecting irrelevant information. We investigated whether the BLA is involved in LI of fear-potentiated startle. Infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5; 12.5 nmoles) into the BLA before preexposure of rats to the neutral stimulus prevent LI of fear-conditioning. We also demonstrated by the same method that a complex of thalamic nuclei, comprising the medial part of the medial geniculate nucleus, the posterior intralaminar nucleus, and the suprageniculate nucleus, is involved in fear-conditioning, but not in LI. This suggests that the presentation of an innocuous stimulus during preexposure leads to an NMDA receptor-dependent change of neurotransmission in the BLA, but not in the thalamus. Our data show that the BLA but not the thalamus regulates in LI of fear-potentiated startle. Furthermore, it supports the hypothesis that the inability of schizophrenic patients to ignore irrelevant stimuli may be caused by hypofunction of the glutamatergic transmission in the brain and suggests an involvement of the amygdala in the neuropathology of schizophrenia.

Lesions of the nucleus basalis magnocellularis do not impair prepulse inhibition and latent inhibition of fear-potentiated startle in the rat.

The present study tested if lesions of the nucleus basalis magnocellularis (NBM) affect prepulse inhibition (PPI) of the acoustic startle response and latent inhibition (LI) of fear-potentiated startle. The NBM is known to play an important role in learning and memory. Recently, the interest of research focused on its role in attentional and response selection processes. We here tested the effect of excitotoxic NBM-lesions on PPI, a phenomenon of sensorimotor gating that occurs at early stages of information processing. We also assessed the lesion effects on LI, a phenomenon of reduced conditioning after stimulus preexposure that can be used to measure selective attention. Bilateral infusions into the NBM of 80 nmol of quinolinic acid markedly reduced the number of choline acetyltransferase immunopositive neurons in the NBM and lead to a pronounced reduction of acetylcholine esterase in the cortex and the amygdala. However, no effects on PPI, fear-conditioning, or LI of fear-potentiated startle were found. Therefore, we conclude that there is no NBM-driven attentional or response selection process involved in PPI. Furthermore, the simple association learning in the classical conditioning paradigm used for fear-potentiated startle or LI is unaffected by NBM-lesions.

Latent inhibition of fear potentiated startle in rats.

Non-reinforced pre-exposure to a prospective conditioned stimulus impairs subsequent conditioning. This phenomenon is termed latent inhibition. In this report, we demonstrate latent inhibition in a classical conditioning procedure, the fear-potentiated startle reflex. Normally, the startle response is enhanced in the presence of a conditioned stimulus that has previously been paired with an aversive stimulus. We show that fear-potentiation of the startle response is significantly less pronounced in rats that have been repeatedly pre-exposed to a conditioned light stimulus. Similar to other procedures reported in the literature, the administration of the psychostimulant drug amphetamine (1.0 mg/kg) before pre-exposure and conditioning disrupts latent inhibition. A good deal is known about the neuronal mechanisms underlying the acquisition and expression of fear-potentiated startle, and therefore this new procedure could be a useful tool for investigating the neuronal basis of latent inhibition.