Faculty Bibliography

The amygdala is located in the medial aspects of the temporal lobe. In spite of the fact that the amygdala has been implicated in a variety of functions, ranging from attention to memory to emotion, it has not attracted neuroscientists to the same extent as its laminated neighbours, in particular the hippocampus and surrounding cortex. However, recently, principles of information processing within the amygdala, particularly in the rat, have begun to emerge from anatomical, physiological and behavioral studies. These findings suggest that after the stimulus enters the amygdala, the highly organized intra-amygdaloid circuitries provide a pathway by which the representation of a stimulus becomes distributed in parallel to various amygdaloid nuclei. As a consequence, the stimulus representation may become modulated by different functional systems, such as those mediating memories from past experience or knowledge about ongoing homeostatic states. The amygdaloid output nuclei, especially the central nucleus, receive convergent information from several other amygdaloid regions and generate behavioral responses that presumably reflect the sum of neuronal activity produced by different amygdaloid nuclei

Projections from the medial geniculate body (MGB) to the lateral nucleus of the amygdala (LA) have been implicated in the conditioning of emotional reactions to acoustic stimuli. Anatomical and physiological studies indicate that this pathway uses the excitatory amino acid L-glutamate as a transmitter. Recent physiological studies have demonstrated that synaptic transmission in the thalamo-amygdala pathway requires the activation of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, two of the major classes of ionotrophic glutamate receptors. In order to characterize the nature of thalamoamygdala interactions, we examined the synaptic associations between thalamic afferents and amygdala neurons that contain at least one glutamate receptor subtype. Thalamic afferents to the amygdala were identified by lesion-induced anterograde degeneration and anterograde transport of biotinylated dextran-amine, while postsynaptic glutamate receptors were labeled immunocytochemically using antisera directed the R1 subunit of the NMDA receptor and the GluR1 and GluR2/3 subunits of the AMPA receptors. Both methods demonstrated that the majority (77%) of thalamic afferents contact dendritic spines, and most (60%) of these spines express at least one glutamate receptor subtype. To a lesser extent, identified afferents also contacted small and large dendritic shafts, and many of these were immunoreactive. Thalamic afferents terminated on approximately the same proportion (60%) of immunoreactive targets for each glutamate receptor studied. These data provide morphological evidence that thalamic afferents directly synapse onto amygdala neurons that express glutamate receptors and suggest ways in which thalamic afferents activate and influence amygdala circuitry

Single neurons were recorded in freely behaving rats during fear conditioning from areas of auditory cortex that project to the lateral nucleus of the amygdala (LA). The latency and rate of conditioning and extinction were analyzed, and the results were compared to previous recordings from LA itself. Auditory cortex neurons took more trials to learn, and they responded more slowly than LA neurons within trials. Short-latency plasticity in LA, therefore, reflects inputs from the auditory thalamus rather than the auditory cortex. Unlike LA cells, some auditory cortex cells showed late conditioned responses that seemed to anticipate the unconditioned stimulus, while others showed extinction-resistant memory storage. Thus, rapid conditioning of fear responses to potentially dangerous stimuli depends on plasticity in the amygdala, while cortical areas may be particularly involved in higher cognitive (mnemonic and attentional) processing of fear experiences

Rats treated with the AMPA receptor-facilitating drug 1-(quinoxolin-6-ylcarbonyl)piperidine (BDP-12) during training acquired fear conditioning to a tone faster than vehicle-treated controls. The effect on acquisition was dependent on the dose given. BDP-12-treated rats and vehicle-treated controls reached the same level of conditioned fear and extinguished at the same rate. The dissociation of learning rate from these other normally covariant measures suggests that the drug had a specific and isolated effect on acquisition. Controls for drug effects on stimulus sensitivity, locomotor activity, generalized fearfulness, and other performance factors support this interpretation. The known action of BDP-12 on receptor dynamics suggests that its effect on acquisition may be attributed to specific modulation of an AMPA and NMDA receptor-dependent plasticity mechanism. The finding that the drug accelerates acquisition but does not affect the level of conditioned fear acquired parallels the effect of the drug on long-term potentiation (LTP) (increasing the rate but not the ceiling of potentiation) and suggests that common mechanisms may underlie fear conditioning and LTP

The GABAa agonist, muscimol (0.5 microgram in 0.5 microliter saline), or vehicle was infused into the lateral and basal amygdala nuclei prior to fear conditioning or testing in rats. Rats given muscimol before conditioning and saline before testing showed much less freezing to the conditioned stimulus (CS) and the context than did controls given saline before training and testing. Rats given saline before training and muscimol prior to testing also showed low levels of freezing to the CS and the context. In follow-up procedures, rats with acquisition initially blocked by pretraining muscimol infusions froze in a manner similar to that of controls when retrained and retested with saline infusions. Rats trained with saline but tested with muscimol presumably became conditioned but could express the learning. When retested with saline, they froze in the same manner as controls. Thus, activity in the lateral and basal amygdala appears to play an essential role in the acquisition and expression of fear conditioning

Recent discoveries about the neural system and cellular mechanisms in pathways mediating classical fear conditioning have provided a foundation for pursuing concurrent connectionist models of this form of emotional learning. The models described are constrained by the known anatomy underlying the behavior being simulated. To date, implementations capture salient features of fear learning, both at the level of behavior and at the level of single cells, and additionally make use of generic biophysical constraints to mimic fundamental excitatory and inhibitory transmission properties. Owing to the modular nature of the systems model, biophysical modeling can be carried out in a single region, in this case the amygdala. Future directions include application of the biophysical model to questions about temporal summation in the two sensory input paths to amygdala, and modeling of an attentional interrupt signal that will extend the emotional processing model to interactions with cognitive systems

Information flow within the intra-amygdaloid circuitry has been generally believed to be unidirectional rather than reciprocal, in which case sensory inputs entering the amygdala via the lateral nucleus would not be modulated by inputs from other amygdaloid regions. In the present study we extend our earlier findings which indicated that the lateral nucleus of the rat amygdala is reciprocally connected with the basal and accessory basal nuclei. The type of synaptic contacts made by these connections is also characterized at the ultrastructural level. An anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into the basal (n=22) or accessory basal nuclei (n=12) of the rat amygdala. The results demonstrate that the ventrolateral division of the lateral nucleus receives projections from the basal nucleus, while the medial division receives projections from the accessory basal nucleus. Electron microscopic analyses revealed that axons projecting from the basal nucleus formed both asymmetric and symmetric contacts within the ventrolateral division of the lateral nucleus, whereas axons projecting from the accessory basal nucleus to the medial division of the lateral nucleus formed only asymmetric synapses with their targets. These findings suggest that the lateral nucleus receives both inhibitory and excitatory intra-amygdaloid projections and indicate that information flow within the amygdala is not unidirectional as previously thought. The results of this study provide evidence that the early phase of sensory processing within the amygdala is already modified by inputs from other amygdaloid nuclei