Faculty Bibliography

A central question in the study of LTP has been to determine what role it plays in memory formation and storage. One valuable form of learning for addressing this issue is associative fear conditioning. In this paradigm an animal learns to associate a tone and shock, such that subsequent presentation of a tone evokes a fear response (freezing behavior). Recent studies indicate that overlapping cellular processes underlie fear conditioning and LTP. The fear response has generally been scored manually which is both labor-intensive and subject to potential artifacts such as inconsistent or biased results. Here we describe a simple automated method that provides unbiased and rapid analysis of animal motion. We show that measured motion, in units termed significant motion pixels (SMPs), is both linear and robust over a wide range of animal speeds and detection thresholds and scores freezing in a quantitatively similar manner to trained human observers. By comparing the frequency distribution of motion during baseline periods and to the response to fox urine (which causes unconditioned fear), we suggest that freezing and non-freezing are distinct behaviors. Finally, we show how this algorithm can be applied to a fear conditioning paradigm yielding information on long and short-term associative memory as well as habituation. This automated analysis of fear conditioning will permit a more rapid and accurate assessment of the role of LTP in memory

In the standard model of pavlovian fear learning, sensory input from neutral and aversive stimuli converge in the lateral nucleus of the amygdala (LA), in which alterations in synaptic transmission encode the association. During fear expression, the LA is thought to engage the central nucleus of the amygdala (CE), which serves as the principal output nucleus for the expression of conditioned fear responses. In the present study, we reexamined the roles of LA and CE. Specifically, we asked whether CE, like LA, might also be involved in fear learning and memory consolidation. Using functional inactivation methods, we first show that CE is involved not only in the expression but also the acquisition of fear conditioning. Next, we show that inhibition of protein synthesis in CE after training impairs fear memory consolidation. These findings indicate that CE is not only involved in fear expression but, like LA, is also involved in the learning and consolidation of pavlovian fear conditioning

What brain regions are involved in regulating behavior when the emotional consequence of a stimulus changes from harmful to harmless? One way to address this question is to study the neural mechanisms underlying extinction of Pavlovian fear conditioning, an important form of emotional regulation that has direct relevance to the treatment of human fear and anxiety disorders. In fear extinction, the capacity of a conditioned stimulus to elicit fear is gradually reduced by repeatedly presenting it in the absence of any aversive consequence. In recent years there has been a dramatic increase in research on the brain mechanisms of fear extinction. One region that has received considerable attention as a component of the brain's extinction circuitry is the medial prefrontal cortex (mPFC). In the present article, we review the historical foundations of the modern notion that the mPFC plays a critical role in emotional regulation, a literature that was largely responsible for studies that explored the role of the mPFC in fear extinction. We also consider the role of the mPFC in a broader neural circuit for extinction that includes the amygdala and hippocampus

Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine-associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin-immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory

Intrusive memories resulting from an emotional trauma are a defining feature of posttraumatic stress disorder (PTSD). Existing studies demonstrate that an increase of noradrenergic activity during a life-threatening event contributes to strengthening or 'overconsolidation' of the memory for trauma. The lateral nucleus of the amygdala (LA) is critical for fear learning. Using classical fear conditioning in rats, we have recently demonstrated that noradrenergic blockade in the LA following reactivation of fear memory by retrieval disrupts memory reconsolidation and lastingly impairs fear memory. This suggests that noradrenergic blockade may be useful in attenuating traumatic memories, even well-consolidated old memories, in PTSD