Faculty Bibliography

Pavlovian fear conditioning has emerged as a leading behavioral paradigm for studying the neurobiological basis of learning and memory. Although considerable progress has been made in understanding the neural substrates of fear conditioning at the systems level, until recently little has been learned about the underlying cellular and molecular mechanisms. The success of systems-level work aimed at defining the neuroanatomical pathways underlying fear conditioning, combined with the knowledge accumulated by studies of long-term potentiation (LTP), has recently given way to new insights into the cellular and molecular mechanisms that underlie acquisition and consolidation of fear memories. Collectively, these findings suggest that fear memory consolidation in the amygdala shares essential biochemical features with LTP, and hold promise for understanding the relationship between memory consolidation and synaptic plasticity in the mammalian brain

The present study applied a visual half field paradigm with emotional facial expressions in patients with selective unilateral amygdalo-hippocampectomy (AHE) to elucidate the contributions of the left and right medial temporal lobe and amygdala to emotional learning. Electrodermal indicators of aversive learning were studied in 14 left AHE and 12 right AHE patients, as well as 13 controls matched in sex and age. In a differential conditioning paradigm with negative (CS+) and positive (CS-) facial expressions, CS+ were associated with an aversive vocalization (US, 95 dB, 3 s). During extinction, stimuli were presented laterally and preattentively using backward masking. Appropriate CS durations yielding preattentive presentation were individually determined prior to conditioning. In contrast to controls, both left and right AHE patients failed to show an autonomic conditioning effect following left visual field presentations of masked negative CS+ during extinction. AHE patients also showed no clear differential acquisition. Moreover, right AHE patients poorly recognised that negative valence was an affiliating dimension of the CS-US compound

Fear conditioning is a form of associative learning in which subjects come to express defense responses to a neutral conditioned stimulus (CS) that is paired with an aversive unconditioned stimulus (US). Considerable evidence suggests that critical neural changes mediating the CS-US association occur in the lateral nucleus of the amygdala (LA). Further, recent studies show that associative long-term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that drugs that interfere with this LTP also disrupt behavioral fear conditioning when infused into the LA, suggesting that associative LTP in LA might be a mechanism for storing memories of the CS-US association. Here, we develop a detailed cellular hypothesis to explain how neural responses to the CS and US in LA could induce LTP-like changes that store memories during fear conditioning. Specifically, we propose that the CS evokes EPSPs at sensory input synapses onto LA pyramidal neurons, and that the US strongly depolarizes these same LA neurons. This depolarization, in turn, causes calcium influx through NMDA receptors (NMDARs) and also causes the LA neuron to fire action potentials. The action potentials then back-propagate into the dendrites, where they collide with CS-evoked EPSPs, resulting in calcium entry through voltage-gated calcium channels (VGCCs). Although calcium entry through NMDARs is sufficient to induce synaptic changes that support short-term fear memory, calcium entry through both NMDARs and VGCCs is required to initiate the molecular processes that consolidate synaptic changes into a long-term memory

Single-cell activity was recorded in the dorsal subnucleus of the lateral amygdala (LAd) of freely behaving rats during Pavlovian fear conditioning, to determine the relationship between neuronal activity and behavioral learning. Neuronal responses elicited by the conditioned stimulus typically increased before behavioral fear was evident, supporting the hypothesis that neural changes in LAd account for the conditioning of behavior. Furthermore, two types of these rapidly modified cells were found. Some, located in the dorsal tip of LAd, exhibited short-latency responses (<20 ms) that were only transiently changed. A second class of cells, most commonly found in ventral regions of LAd, had longer latency responses, but maintained enhanced responding throughout training and even through extinction. These anatomically distinct cells in LAd may be differentially involved in the initiation of learning and long-term memory storage

It is well established that the amygdala plays an essential role in Pavlovian fear conditioning, with the lateral nucleus serving as the interface with sensory systems that transmit the conditioned stimulus and the central nucleus as the link with motor regions that control conditioned fear responses. The lateral nucleus connects with the central nucleus directly and by way of several other amygdala regions, including the basal, accessory basal, and medial nuclei. To determine which of these regions is necessary, and thus whether conditioning requires the direct or one of the indirect intra-amygdala pathways, we made lesions in rats of the lateral, central, basal, accessory basal, and medial nuclei, as well as combined lesions of the basal and accessory basal nuclei and of the entire amygdala. Animals subsequently underwent fear conditioning trials in which an auditory conditioned stimulus was paired with a footshock unconditioned stimulus. Animals that received lesions of the lateral or central nucleus, or of the entire amygdala, were dramatically impaired, whereas the other lesions had little effect. These findings show that only the lateral and central nuclei are necessary for the acquisition of conditioned fear response to an auditory conditioned stimulus

This article is a transcription of an electronic symposium in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the neurobiology of emotion. Four basic questions were debated: 1) What are the most critical issues/questions in the neurobiology of emotion? 2) What do we know for certain about brain processes involved in emotion and what is controversial? 3) What kinds of research are needed to resolve these controversial issues? 4) What is the relationship between learning, memory and emotion? The focus was on the existence of different neural systems for different emotions and the nature of the neural coding for the emotional states. Is emotion the result of the interaction of different brain regions such as the amygdala, the nucleus accumbens, or the periaqueductal gray matter or is it an emergent property of the whole brain neural network? The relationship between unlearned and learned emotions was also discussed. Are the circuits of the former the underpinnings of the latter? It was pointed out that much of what we know about emotions refers to aversively motivated behaviors, like fear and anxiety. Appetitive emotions should attract much interest in the future. The learning and memory relationship with emotions was also discussed in terms of conditioned and unconditioned stimuli, innate and learned fear, contextual cues inducing emotional states, implicit memory and the property of using this term for animal memories. In a general way it could be said that learning modifies the neural circuits through which emotional responses are expressed

Projections to the amygdala from various cortical and subcortical areas terminate in different nuclei. In the present study we examined long-term potentiation of synaptic transmission in the lateral or the basal amygdaloid nuclei by theta burst stimulation of thalamic vs. cortical sensory projections in the anesthetized rat. Although both the medial geniculate nucleus and the dorsal perirhinal cortex have direct projections to lateral nucleus, only the thalamic stimulation induced long-term potentiation of field potentials recorded in the lateral nucleus. In contrast, cortical (ventral perirhinal cortex) but not thalamic stimulation induced long-term potentiation in the basal nucleus.Since the thalamic pathway is believed to process simple/unimodal stimulus features, and the perirhinal cortex complex/polymodal sensory representations, the dissociation of long-term potentiation in lateral and basal nuclei suggests that the basal nucleus may serve as an amygdaloid sensory interface for complex stimulus information similar to the role of the lateral nucleus in relation to relatively simple representations. Thus plasticity of simple and complex representations may involve different amygdala inputs and circuits