Faculty Bibliography

Traditional accounts of the self represented in religion, literature, philosophy, and other branches of the humanities, are grounded in the subject's personal introspections. This source of knowledge has had a profound impact on terminology, concepts, and theories of the self. By contrast, the scientific method, which uses observational and experimental data, is aimed at objective analyses. The scientific approach to the self, by its very nature, is distinct from the approach in the humanities, and therefore reveals a different view of the self, and sparks new debate about what the self really is. Moreover, different scientific disciplines, spanning the natural and social sciences, investigate different levels of organization, leading to a multifaceted scientific picture of the self. This conference and volume explored areas where some of the different approaches to the self overlap and will, it is hoped, promote the establishment of a richer, more coherent image of what the self is

Can we find a way of thinking about the self that is compatible with modern neuroscience? I think we can. First of all, we have to recognize that 'the self' is not the same as 'the conscious self,' since much of who we are as individuals takes place out of conscious awareness. Second, we have to accept that some aspects of the self, especially the unconscious aspects, occur in and can be studied in other species, allowing us to relate these aspects of the self to detailed brain mechanisms. Finally, it also helps to think of the self in terms of memory. Obviously, much of who we are is based on memories learned through personal experience, including both conscious or explicit memories and unconscious or implicit memories. This is particularly important since much progress has been made in relating memory to the cells and synapses of the brain. By viewing the self as a network of memories the effort to relate the self to the brain can build on this progress. Emphasizing memory and experience does not take away from the fact that our genetic history also contributes to who we are. In fact, genes and experience, or nature and nurture, are, in the end, not different things, but different ways of doing the same thing-wiring the synapses of our brain. In many ways, the self is synaptic. This synaptic view of the self is not meant as a challenge to other views, such as spiritual, cultural, or psychological views. It is instead, just a way of understanding how these other aspects of who we are relate, deep down, to the brain

1. Considerable progress has been made over the past 20 years in relating specific circuits of the brain to emotional functions. Much of this work has involved studies of Pavlovian or classical fear conditioning, a behavioral procedure that is used to couple meaningless environmental stimuli to emotional (defense) response networks. 2. The major conclusion from studies of fear conditioning is that the amygdala plays critical role in linking external stimuli to defense responses. 3. Before describing research on the role of the amygdala in fear conditioning, though, it will be helpful to briefly examine the historical events that preceded modern research on conditioned fear

Long-term memory underlying Pavlovian fear conditioning is believed to involve plasticity at sensory input synapses in the lateral nucleus of the amygdala (LA). A useful physiological model for studying synaptic plasticity is long-term potentiation (LTP). LTP in the LA has been studied only in vitro or in anaesthetized rats. Here, we tested whether LTP can be induced in auditory input pathways to the LA in awake rats, and if so, whether it persists over days. In chronically implanted rats, extracellular field potentials evoked in the LA by stimulation of the auditory thalamus and the auditory association cortex, using test simulations and input/output (I/O) curves, were compared in the same animals after tetanization of either pathway alone or after combined tetanization. For both pathways, LTP was input-specific and long lasting. LTP at cortical inputs exhibited the largest change at early time points (24 h) but faded within 3 days. In contrast, LTP at thalamic inputs, though smaller initially than cortical LTP, remained stable until at least 6 days. Comparisons of I/O curves indicated that the two pathways may rely on different mechanisms for the maintenance of LTP and may benefit differently from their coactivation. This is the first report of LTP at sensory inputs to the LA in awake animals. The results reveal important characteristics of synaptic plasticity in neuronal circuits of fear memory that could not have been revealed with in vitro preparations, and suggest a differential role of thalamic and cortical auditory afferents in long-term memory of fear conditioning

BACKGROUND: Panic attacks, the hallmark of panic disorder, are often characterized by hyperventilation. Existing animal models of anxiety have not addressed the effects of the hyperventilation on anxiety-related behaviors. Doxapram is a respiratory stimulant that reliably evokes panic attacks in patients with panic disorder. We examined doxapram in four rodent models of anxiety and sought to identify brain regions involved in its behavioral effects. METHODS: The effects of doxapram were determined for cue and contextual fear conditioning, the open field test, and the social interaction test. The effect of doxapram on c-Fos-like immunoreactivity was examined in three brain regions. RESULTS: Doxapram at 4 mg/kg increased anxiety-related behaviors in all four anxiety models. An inverted U-shaped dose-response curve was identified for fear conditioning to cue. Doxapram induced c-Fos-like immunoreactivity in the central nucleus of the amygdala but not the lateral nucleus or the nucleus tractus solitarius. CONCLUSIONS: Doxapram enhanced anxiety-related behaviors in four animal models of anxiety that involve conditioning or spontaneous avoidance. The effect of doxapram may result from activation of neurons in the amygdala. Doxapram, by inducing hyperventilation, may be a useful adjunct to existing animal anxiety models for improving validity for panic anxiety

We recorded neurons from the hippocampus of freely behaving rats during an auditory fear conditioning task. Rats received either paired or unpaired presentations of an auditory conditioned stimulus (CS) and an electric shock unconditioned stimulus (US). Hippocampal neurons (place and theta cells) acquired responses to the auditory CS in the paired but not in the unpaired group. After CS-US pairing, rhythmic firing of theta cells became synchronized to the onset of the CS. Conditioned responses of place cells were gated by their location-specific firing, so that after CS-US pairing, place cells responded to the CS only when the rat was within the cell's place field. These findings may help to elucidate how the hippocampus contributes to context-specific memory formation during associative learning