Faculty Bibliography

Projections to the amygdala from the auditory thalamus have been implicated in the associative conditioning of fear responses to acoustic stimuli. Thalamo-amygdala auditory projections enter the amygdala via the lateral nucleus (LA). It is well documented that these projections originate in the medial division (MGm) of the medial geniculate nucleus (MGN), the posterior intralaminar nucleus (PIN), and the suprageniculate nucleus (Sg). It is not known, however, whether these thalamic projections terminate in a topographic fashion within the LA. We therefore used several retrograde tract tracing techniques to determine whether the terminations of thalamo-amygdala fibers have a topographic organization within the LA. These tracers were injected into various locations within the LA, and the distribution of the retrogradely labeled cells throughout the thalamus was analyzed. In general, rostral to caudal distinctions in the thalamus are maintained in the LA, such that projections from throughout the MGN terminate in the anterior part of the LA, whereas the caudal part of the MGN projects to the caudal part of the LA. Furthermore, the density of cells that give rise to thalamo-amygdala projections varies within each thalamic nucleus along the rostro-caudal axis. The patterns of thalamo-amygdala connectivity observed support previous parcellation schemes that segregate the LA into dorsal, medial, and lateral areas, and suggest that the LA should be further divided into anterior and posterior parts. In addition to the well-known projections to the LA originating from PIN, MGN, and Sg, we also found substantial projections from the dorsal portion of the MGN (MGd) and the lateral posterior thalamic nucleus (LP). These findings suggest that some of the functional segregation in the thalamus may be preserved in the LA, and that the role of the MGd and LP in thalamo-amygdala transmission should be reconsidered

The lateral nucleus of the amygdala (LA) is a critical component of the circuitry through which environmental stimuli are endowed with emotional meaning through association with painful or threatening events. Individual cells in LA receive convergent input from auditory processing areas in the thalamus and cortex, and the excitatory amino-acid L-glutamate (Glu) participates in synaptic transmission in both pathways. Previously, we characterized the ultrastructure of pre- and postsynaptic processes in the thalamo-amygdala pathway, and showed the relation of presynaptic inputs to N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydoxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits. In the present study, we examined the nature of cortico-amygdala synaptic interactions with Glu receptors in LA and determined whether they are similar or different from those in the thalamo-amygdala pathway. Cortical afferents to the LA were identified by anterograde transport of biotinylated-dextran amine (BDA) and postsynaptic sites were labeled immunocytochemically using antisera directed against the R1 subunit the NMDA receptor, and the R1 and R2/3 subunits of the AMPA receptor. Electron microscopy revealed that the vast majority of cortical afferents (99%) synapse onto distal dendritic processes and most of these processes (62%) contained at least one glutamate receptor subtype. Cortical afferents synapsed on approximately the same proportion of immunoreactive targets for each glutamate receptor subtype examined. These data provide morphological evidence that cortical afferents form direct synaptic contacts with LA neurons that express both NMDA and AMPA receptors and are consistent with recent physiological studies demonstrating the participation of NMDA and AMPA receptors in cortico-amygdala-transmission. These results are nearly identical to those obtained in the studies of the thalamo-amygdala pathway

It is commonly assumed that suppression of an ongoing behavior is an indirect measure of freezing behavior. We tested whether conditioned suppression and freezing are the same or distinct conditioned responses. Rats were trained to press a bar for food and then given fear-conditioning sessions in which a tone was paired with a foot shock (two pairings a day for 2 days). They then received either sham or electrolytic lesions of the periaqueductal gray (PAG). Post-training PAG lesions blocked freezing to the conditioned stimulus (CS), but had no effect on the suppression of operant behavior to the same CS. Thus, conditioned suppression and freezing, which both cause a cessation in activity, appear to be mediated by separate processes

Neurons in the lateral amygdala (LA) receive glutamatergic sensory input from the auditory thalamus and auditory cortex, and these inputs can be modulated by serotonin (5-HT). In the present study, we examined whether serotonergic inhibition of glutamatatergic excitation in the LA occurs via activation of GABAergic interneurons. Single-unit extracellular activity in the LA was recorded in response to iontophoretically applied glutamate. Concurrent application of 5-HT reduced the number of glutamate-evoked action potentials in the majority of neurons tested. GABA antagonists were then iontophoresed with both glutamate and 5-HT. Of the neurons that were inhibited by 5-HT, concurrent application of the GABA antagonists significantly reversed this effect. Application of the GABA antagonists alone had little or no effect on basal neuronal activity. We conclude that the 5-HT-induced inhibition of glutamatergic activity occurs in part through activation of serotonergic receptors on GABAergic interneurons

Fear conditioning has received extensive experimental attention. However, little is known about the molecular mechanisms that underlie fear memory consolidation. Previous studies have shown that long-term potentiation (LTP) exists in pathways known to be relevant to fear conditioning and that fear conditioning modifies neural processing in these pathways in a manner similar to LTP induction. The present experiments examined whether inhibition of protein synthesis, PKA, and MAP kinase activity, treatments that block LTP, also interfere with the consolidation of fear conditioning. Rats were injected intraventricularly with Anisomycin (100 or 300 microg), Rp-cAMPS (90 or 180 microg), or PD098059 (1 or 3 microg) prior to conditioning and assessed for retention of contextual and auditory fear memory both within an hour and 24 hr later. Results indicated that injection of these compounds selectively interfered with long-term memory for contextual and auditory fear, while leaving short-term memory intact. Additional control groups indicated that this effect was likely due to impaired memory consolidation rather than to nonspecific effects of the drugs on fear expression. Results suggest that fear conditioning and LTP may share common molecular mechanisms

Fear conditioning involves the transmission of sensory stimuli to the amygdala from the thalamus and cortex. These input synapses are prime candidates for sites of plasticity critical to the learning in fear conditioning. Because N-methyl-D-aspartate (NMDA)-dependent mechanisms have been implicated in fear learning, we investigated the contribution of NMDA receptors to synaptic transmission at putative cortical and thalamic inputs using visualized whole cell recording in amygdala brain slices. Whereas NMDA receptors are present at both of these pathways, differences were observed. First, the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated component of the synaptic response, relative to the NMDA component, is smaller at thalamic than cortical input synapses. Second, thalamic NMDA responses are more sensitive to Mg2+. These findings suggest that there are distinct populations of NMDA receptors at cortical and thalamic inputs to the lateral amygdala. Differences such as these might underlie unique contributions of the two pathways to fear conditioning

Comments on M. Solms and E. Nersessian's (see record 2000-02440-001) target article on Freud's theory of affect and its possible neuroanatomical, physiological, and chemical correlates. J. LeDoux discusses several points made by Solms and Nersessian in order to do a translation of some of their notions in terms related to modern work on the brain mechanisms of emotion and cognition. LeDoux also comments briefly on J. Panksepp's (see article 2000-02440-002) discussion of Solms and Nersessian's article. (PsycINFO Database Record (c) 2008 APA, all rights reserved)

Past studies examining the contributions of dopamine to fear have produced inconsistent results. The present experiments reevaluated this issue. It was found that systemic pretreatment with the D2 agonist quinpirole before pairing 2 conditioned stimuli (CSs; CS2-CS1) dose dependently blocked the acquisition of second-order fear conditioning. Quinpirole's actions were not due to nonspecific impairments in the ability to perceive the CSs, or form and store an association, because the identical drug pretreatment before pairing the same 2 CSs had no effect on the acquisition of sensory preconditioning. In a separate study, rats were given fear conditioning while untreated and then received extinction sessions while under the influence of quinpirole or its vehicle. Quinpirole pretreatment blocked extinction. Findings suggest that quinpirole decreased fear by blocking the retrieval of a learned association between a CS and unconditioned stimulus (UCS), rather than by devaluing the UCS, which would have resulted from summation of quinpirole's appetitive properties with the aversive properties of fear. (PsycINFO Database Record (c) 2008 APA, all rights reserved) (journal abstract)