Faculty Bibliography

The effects of entorhinal cortex lesions, combined entorhinal and perirhinal cortex lesions, and fornix lesions on the conditioning of fear responses (freezing) to contextual stimuli were examined using a conditioning procedure known to produce hippocampal-dependent contextual conditioning. Lesions of the entorhinal and or entorhinal plus perirhinal cortex did not disrupt contextual conditioning, but lesions of the fornix did. None of the lesions affected conditioning to an explicit conditioned stimulus. Given that the entorhinal cortex is the primary linkage between the neocortex and the hippocampus and that the fornix is the primary linkage with subcortical structures, subcortical inputs to and outputs of the hippocampus appear to be sufficient to mediate contextual fear conditioning. As a result, the presumption that neocortical information is required for contextual fear conditioning, and perhaps other hippocampal-dependent functions, should be reevaluated

Transmission of auditory information from the medial geniculate body to the lateral nucleus of the amygdala is believed to be involved in the conditioning of fear responses to acoustic stimuli. This pathway exhibits LTP of electrically evoked field potentials after high frequency stimulation of the medial geniculate body. High frequency stimulation of the medial geniculate body also results in a long-lasting potentiation of a field potential in the lateral amygdala elicited by a naturally transduced acoustic stimulus. This demonstrates that natural information processing can make use of the physiological mechanisms set in motion by LTP induction

The amygdaloid complex receives sensory information from a variety of sources. A widely held view is that the amygdaloid complex utilizes this information to orchestrate appropriate species-specific behaviors to ongoing experiences. Relatively little is known, however, about the circuitry through which information is processed within the amygdaloid complex. The lateral nucleus is the major recipient of extrinsic sensory information and is the origin of many intra-amygdaloid projections. In this study, we reinvestigated the organization of intra-amygdaloid projections originating from the lateral nucleus using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The lateral nucleus has highly organized intranuclear connections. Dense projections interconnect rostral and caudal levels of the lateral and the medial divisions of the nucleus, and the lateral and medial divisions of the lateral nucleus are also interconnected. The major extranuclear projections of the lateral nucleus are (in descending order of magnitude) to the accessory basal nucleus, the basal nucleus, the periamygdaloid cortex, the dorsal portion of the central division of the medial nucleus, the posterior cortical nucleus, the capsular division of the central nucleus, and the lateral division of the amygdalohippocampal area. The pattern of extranuclear projections varied depending on the rostrocaudal or mediolateral location of the injection site within the lateral nucleus. These findings indicate that intra-amygdaloid projections originating in the lateral nucleus are both more widespread and more topographically organized than was previously appreciated

Conditioning of fear reactions to an auditory conditioned stimulus (CS) paired with a footshock unconditioned stimulus (US) involves CS transmission to the amygdala from the auditory thalamus, the auditory cortex, or both. This article presents a simple neural network model of this neural system. The model consists of modules of mutually inhibitory nonlinear units representing the different relevant anatomical structures of the thalamo-amygdala and thalamo-corticoamygdala circuitry. Frequency-specific changes produced by fear conditioning were studied at the behavioral level (stimulus generalization) and the single-unit level (receptive fields). The findings mirror effects observed in conditioning studies of animals. This computational model provides an initial grounding for explorations of how emotional information and behavior are related to anatomical and physiological observations

The effects on freezing behavior elicited by contextual and phasic conditioned stimuli (CSs) were examined in rats with septal lesions. Two weeks after surgery, blocks of 2 conditioning trials consisting of a tone (10 kHz, 75 dB, 20 s) paired with a footshock (500 ms, 0.5 mA) were presented on 2 consecutive days. Tone-alone trials were presented each day thereafter until extinction criterion was met. Septal lesions were found to potentiate the freezing response elicited by contextual stimuli but had no effect on freezing elicited by the phasic CS. The septum thus appears to be involved in the acquisition and/or expression of defensive behaviors elicited by contextual stimuli

We examined whether the NMDA class of excitatory amino acid receptors contribute to synaptic transmission in the pathway connecting the medial geniculate body (MGB) with the lateral nucleus of the amygdala (LA) using extracellular single unit recordings and microiontophoresis. Cells were identified in LA on the basis of responsivity to electrical stimulation of the MGB. For each cell, a level of current was found for the iontophoretic ejection of the NMDA antagonist AP5 that blocked responses elicited by iontophoresis of NMDA, but had no effect on responses elicited by AMPA. Iontophoresis of AP5 with this level of current blocked the excitatory response elicited by MGB stimulation in most cells tested. Microinfusion of AP5 (25, 50, or 100 microM) also blocked the responses. Additional studies tested individual cells with both AP5 and the AMPA antagonist CNQX and showed that blockade of either NMDA or AMPA receptors interferes with synaptic transmission. Finally, iontophoretic ejection of either AP5 or CNQX blocked short-latency (< 25 ms) responses elicited in LA by peripheral auditory stimulation. Together, these results suggest that the synaptic evocation of action potentials in the thalamo-amygdala pathway depends on both NMDA and non-NMDA receptors. We hypothesize that non-NMDA receptors are most likely required to depolarize the cell sufficiently to remove the blockade of NMDA channels by magnesium and NMDA receptors are required to further depolarize the membrane to the level required for action potential generation