The many paths to fear

Abstract

Fear is an emotion that has powerful effects on behaviour and physiology across animal species. It is accepted that the amygdala has a central role in processing fear. However, it is less widely appreciated that distinct amygdala outputs and downstream circuits are involved in different types of fear. Data show that fear of painful stimuli, predators and aggressive members of the same species are processed in independent neural circuits that involve the amygdala and downstream hypothalamic and brainstem circuits. Here, we discuss data supporting multiple fear pathways and the implications of this distributed system for understanding and treating fear.

GAL 3 receptor KO mice exhibit an anxiety-like phenotype

“…In the mouse brain, GAL 3 receptor mRNA and protein are prominently expressed in the periaqueductal gray, thalamus, hypothalamus, amygdala, hippocampal formation, and prefrontal cortex (10,11), which are brain areas that play an important role in emotional regulation and stress sensitivity. It is likely that GAL modulates stress and anxiety through GAL 3 receptors located in the hypothalamus, either by directly modulating neuronal circuitries involving the amygdala, hippocampus, raphe nucleus, and locus coeruleus or by interfering with the hypothalamic-pituitary-adrenal axis (33). In addition, the effect of gene deletion during embryogenesis may be compensated for during brain development, which can result in an adult phenotype different from that of acute pharmacological blockade.…”

Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans

“…To evaluate whether Baiap3 genotype would affect the propensity for di- D 1 9 : 1 3 5 -1 4 8 , 2 0 1 3 14.42 ± 3.70 [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] 0.680 (Z = -0.41)…”

“…Baiap3 has a unique and striking expression pattern (Allen Brain Atlas [http://mouse.brainmap.org]) in brain regions such as the central, medial and basomedial amygdaloid nuclei; the hypothalamus; and the periaqueductal gray. These areas are involved in regulating autonomic functions and are also critical in processing fearful stimuli and mediating anxiety-related behaviors (26,27). The cellular function of Baiap3 is currently unknown; however, all other Munc13 members are regulators of vesicle exocytosis in various cell types (28).…”

Participação do sistema histaminérgico em estruturas límbicas sobre a memória de esquiva inibitória em camundongos

“…Learned fear may be elicited by exposure to environmental cues or contexts that were previously associated with an aversive stimuli (Gross and Canteras, 2012). In rodents, an aversive stimulus may be a predator (fear of predators), a conspecific (fear of aggressive conspecifics) or a harmful stimulus, such as a foot-shock.…”

“…Evidence suggests that the encoding of learned fear of aversive stimuli requires projections from the ventrolateral periaqueductal grey (vlPAG), via the thalamus, to the cortical association areas that are involved in the higher-order processing of contextual cues (review Gross and Canteras, 2012). The vlPAG responds to aversive stimuli via ascending projections from the spinal cord and is likely to relay expectancy-modulated information to instruct associative plasticity in the hippocampus and amygdala during fear conditioning to aversive stimuli (Johansen et al, 2010).…”