Basolateral amygdala neurons are activated during threat expectation.

Fear conditioning studies have led to the view that the amygdala contains neurons that signal threat and in turn elicit defensive behaviors through their brain stem and hypothalamic targets. In agreement with this model, a prior unit-recording study in rats performing a seminaturalistic foraging task revealed that many lateral amygdala (LA) neurons are predator responsive. In contrast, our previous study emphasized that most basolateral (BL) amygdala neurons are inhibited at proximity of the predator. However, the two studies used different methods to analyze unit activity, complicating comparisons between them. By applying the same method to the sample of BL neurons we recorded previously, the present study revealed that most principal cells are inhibited by the predator and only 4.5% are activated. Moreover, two-thirds of these cells were also activated by nonthreatening stimuli. In fact, fitting unit activity with a generalized linear model revealed that the only task variables associated with a prevalent positive modulation of BL activity were expectation of the predator's presence and whether the prior trial had been a failure or success. At odds with the threat-coding model of the amygdala, actual confrontation with the predator was usually associated with a widespread inhibition of principal BL neurons. NEW & NOTEWORTHY The basolateral amygdala (BL) is thought to contain neurons that signal threat, in turn eliciting defensive behaviors. In contrast, the present study reports that very few principal BL cells are responsive to threats and that most of them are also activated by nonthreatening stimuli. Yet, expectation of the threat's presence was associated with a prevalent positive modulation of BL activity; actual confrontation with the threat was associated with a widespread inhibition.

[1]  June-Seek Choi,et al.  Amygdala regulates risk of predation in rats foraging in a dynamic fear environment , 2010, Proceedings of the National Academy of Sciences.

[2]  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.

[3]  L. Saksida,et al.  Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala Circuits and Learning-Related Behavior , 2018, Current Biology.

[4]  J. D. McGaugh The amygdala modulates the consolidation of memories of emotionally arousing experiences. , 2004, Annual review of neuroscience.

[5]  Lynn Hazan,et al.  Klusters, NeuroScope, NDManager: A free software suite for neurophysiological data processing and visualization , 2006, Journal of Neuroscience Methods.

[6]  M. Fanselow,et al.  Changes in feeding and foraging patterns as an antipredator defensive strategy: a laboratory simulation using aversive stimulation in a closed economy. , 1988, Journal of the experimental analysis of behavior.

[7]  R. Tibshirani Regression Shrinkage and Selection via the Lasso , 1996 .

[8]  N. Canteras,et al.  Amygdalar roles during exposure to a live predator and to a predator-associated context , 2011, Neuroscience.

[9]  Denis Paré,et al.  When scientific paradigms lead to tunnel vision: lessons from the study of fear , 2017, npj Science of Learning.

[10]  Robert M Sears,et al.  Active Avoidance Requires a Serial Basal Amygdala to Nucleus Accumbens Shell Circuit , 2015, The Journal of Neuroscience.

[11]  Alon Amir,et al.  Vigilance-Associated Gamma Oscillations Coordinate the Ensemble Activity of Basolateral Amygdala Neurons , 2018, Neuron.

[12]  A. McDonald Cortical pathways to the mammalian amygdala , 1998, Progress in Neurobiology.

[13]  J. Zhang,et al.  Noradrenergic innervation of pyramidal cells in the rat basolateral amygdala , 2013, Neuroscience.

[14]  N. Canteras,et al.  What ethologically based models have taught us about the neural systems underlying fear and anxiety , 2012, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[15]  Drew B. Headley,et al.  Amygdala Signaling during Foraging in a Hazardous Environment , 2015, The Journal of Neuroscience.

[16]  Eran Stark,et al.  Large-scale recording of neurons by movable silicon probes in behaving rodents. , 2012, Journal of visualized experiments : JoVE.

[17]  D. Paré,et al.  Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. , 2010, Physiological reviews.

[18]  L. Takahashi,et al.  Medial amygdala modulation of predator odor-induced unconditioned fear in the rat. , 2004, Behavioral neuroscience.

[19]  Jian Huang,et al.  Group descent algorithms for nonconvex penalized linear and logistic regression models with grouped predictors , 2012, Statistics and Computing.

[20]  Sang Geon Park,et al.  Dynamic coding of predatory information between the prelimbic cortex and lateral amygdala in foraging rats , 2018, Science Advances.

[21]  M. Yuan,et al.  Model selection and estimation in regression with grouped variables , 2006 .

[22]  Joseph E LeDoux,et al.  Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding , 2017, The Journal of Neuroscience.

[23]  Michael Davis,et al.  Fear-potentiated startle using an auditory conditioned stimulus: Effect of lesions of the amygdala , 1987, Physiology & Behavior.

[24]  G. Buzsáki,et al.  Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. , 2004, Journal of neurophysiology.

[25]  A. McDonald,et al.  Parvalbumin-containing neurons in the rat basolateral amygdala: morphology and co-localization of Calbindin-D 28k , 2001, Neuroscience.

[26]  Denis Pare,et al.  Impact of Basal Forebrain Cholinergic Inputs on Basolateral Amygdala Neurons , 2015, The Journal of Neuroscience.

[27]  D. Blanchard,et al.  Antipredator defensive behaviors in a visible burrow system. , 1989, Journal of comparative psychology.

[28]  M. Herkenham,et al.  Thalamoamygdaloid projections in the rat: A test of the amygdala's role in sensory processing , 1991, The Journal of comparative neurology.

[29]  D. Paré,et al.  Intra‐amygdaloid projections of the lateral nucleus in the cat: PHA‐L anterograde labeling combined with postembedding GABA and glutamate immunocytochemistry , 1994, The Journal of comparative neurology.

[30]  E J Chichilnisky,et al.  Prediction and Decoding of Retinal Ganglion Cell Responses with a Probabilistic Spiking Model , 2005, The Journal of Neuroscience.

[31]  K. Tye,et al.  From circuits to behaviour in the amygdala , 2015, Nature.

[32]  D. Paré,et al.  Intra-amygdaloid projections of the basolateral and basomedial nuclei in the cat: Phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron microscopic level , 1995, Neuroscience.

[33]  Joseph E LeDoux,et al.  Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala , 1997, Trends in Neurosciences.

[34]  J. Price,et al.  A description of the amygdaloid complex in the rat and cat with observations on intra‐amygdaloid axonal connections , 1978, The Journal of comparative neurology.

[35]  Damaris Zurell,et al.  Collinearity: a review of methods to deal with it and a simulation study evaluating their performance , 2013 .

[36]  G. Quirk,et al.  Neuronal signalling of fear memory , 2004, Nature Reviews Neuroscience.

[37]  Il Memming Park,et al.  Encoding and decoding in parietal cortex during sensorimotor decision-making , 2014, Nature Neuroscience.

[38]  N. Canteras,et al.  Roles of the anterior basolateral amygdalar nucleus during exposure to a live predator and to a predator-associated context , 2018, Behavioural Brain Research.

[39]  Pete C. Trimmer,et al.  Foraging for foundations in decision neuroscience: insights from ethology , 2018, Nature Reviews Neuroscience.

[40]  R. Dielenberg,et al.  Defensive behavior in rats towards predatory odors: a review , 2001, Neuroscience & Biobehavioral Reviews.

[41]  Drew B. Headley,et al.  Multi-dimensional Coding by Basolateral Amygdala Neurons , 2018, Neuron.

[42]  N. Canteras,et al.  The many paths to fear , 2012, Nature Reviews Neuroscience.