Oxytocin Selectively Gates Fear Responses Through Distinct Outputs from the Central Amygdala

Specific neuronal populations in the amygdala control different behavioral and physiological components of the fear response. Central amygdala (CeA) projections to hypothalamic and brain stem nuclei regulate the behavioral and physiological expression of fear, but it is unknown whether these different aspects of the fear response can be separately regulated by the CeA. We combined fluorescent retrograde tracing of CeA projections to nuclei that modulate fear-related freezing or cardiovascular responses with in vitro electrophysiological recordings and with in vivo monitoring of related behavioral and physiological parameters. CeA projections emerged from separate neuronal populations with different electrophysiological characteristics and different response properties to oxytocin. In vivo, oxytocin decreased freezing responses in fear-conditioned rats without affecting the cardiovascular response. Thus, neuropeptidergic signaling can modulate the CeA outputs through separate neuronal circuits and thereby individually steer the various aspects of the fear response.

[1]  Lief E. Fenno,et al.  Amygdala circuitry mediating reversible and bidirectional control of anxiety , 2011, Nature.

[2]  Michael B. Stadler,et al.  Encoding of conditioned fear in central amygdala inhibitory circuits , 2010, Nature.

[3]  David J. Anderson,et al.  Genetic dissection of an amygdala microcircuit that gates conditioned fear , 2010, Nature.

[4]  A. Schwarz,et al.  A Neural Switch for Active and Passive Fear , 2010, Neuron.

[5]  Matthew A. Howard,et al.  The Amygdala Is a Chemosensor that Detects Carbon Dioxide and Acidosis to Elicit Fear Behavior , 2009, Cell.

[6]  R. Sansone,et al.  Panic disorder subtypes: deceptive somatic impersonators. , 2009, Psychiatry (Edgmont (Pa. : Township)).

[7]  K. Tye,et al.  Rapid strengthening of thalamo-amygdala synapses mediates cue–reward learning , 2008, Nature.

[8]  I. Neumann,et al.  Centrally released oxytocin mediates mating-induced anxiolysis in male rats , 2007, Proceedings of the National Academy of Sciences.

[9]  M. Mühlethaler,et al.  Excitatory action of hypocretin/orexin on neurons of the central medial amygdala , 2006, Neuroscience.

[10]  B. Chieng,et al.  Characterization of neurons in the rat central nucleus of the amygdala: Cellular physiology, morphology, and opioid sensitivity , 2006, The Journal of comparative neurology.

[11]  D. Tranel,et al.  Gastric myoelectrical activity as an index of emotional arousal. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[12]  A. Damasio,et al.  Basic emotions are associated with distinct patterns of cardiorespiratory activity. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[13]  F. Champagne,et al.  Stress During Gestation Alters Postpartum Maternal Care and the Development of the Offspring in a Rodent Model , 2006, Biological Psychiatry.

[14]  Joseph J. Paton,et al.  The primate amygdala represents the positive and negative value of visual stimuli during learning , 2006, Nature.

[15]  A. Douglas,et al.  Brain Oxytocin Correlates with Maternal Aggression: Link to Anxiety , 2005, The Journal of Neuroscience.

[16]  P. Veinante,et al.  Vasopressin and Oxytocin Excite Distinct Neuronal Populations in the Central Amygdala , 2005, Science.

[17]  A. Shekhar,et al.  Interactions between NPY and CRF in the amygdala to regulate emotionality , 2004, Neuropeptides.

[18]  S. Porges,et al.  Social Engagement and Attachment , 2003, Annals of the New York Academy of Sciences.

[19]  Joseph E LeDoux.  The Emotional Brain, Fear, and the Amygdala , 2003, Cellular and Molecular Neurobiology.

[20]  D. Paré,et al.  Physiological properties of central amygdala neurons: species differences , 2002, The European journal of neuroscience.

[21]  H. Akil,et al.  Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: Evidence for their selective activation by interleukin‐1β , 1999, The Journal of comparative neurology.

[22]  M. McCarthy,et al.  An Anxiolytic Action of Oxytocin is Enhanced by Estrogen in the Mouse , 1996, Physiology & Behavior.

[23]  M. Behbehani,et al.  An electrophysiological characterization of the projection from the central nucleus of the amygdala to the periaqueductal gray of the rat: the role of opioid receptors , 1995, Brain Research.

[24]  Joseph E LeDoux,et al.  Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  A. Burkhalter,et al.  Fluorescent latex microspheres as a retrograde neuronal marker for in vivo and in vitro studies of visual cortex , 1984, Nature.

[26]  J S Schwaber,et al.  Amygdaloid and basal forebrain direct connections with the nucleus of the solitary tract and the dorsal motor nucleus , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.