scholarly journals The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning

2019 ◽  
Author(s):  
Mattia Aime ◽  
Elisabete Augusto ◽  
Vladimir Kouskoff ◽  
Christelle Martin ◽  
Yann Humeau ◽  
...  
Keyword(s):  
Gaussian Noise ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Fear Learning ◽  
Association Cortex ◽  
Dependent Manner ◽  
Appropriate Behavior ◽  
Frontal Association Cortex ◽  
Time Of Presentation ◽  
New Framework

ABSTRACTSurvival depends on the ability of animals to select the appropriate behavior in response to threat and safety sensory cues. However, the synaptic and circuit mechanisms by which the brain learns to encode accurate predictors of threat and safety remain largely unexplored. Here, we show that frontal association cortex (FrA) pyramidal neurons integrate auditory cues and basolateral amygdala (BLA) inputs non-linearly in a NMDAR-dependent manner. We found that the response of FrA pyramidal neurons was more pronounced to Gaussian noise than to pure 8 kHz tone, and that the activation of BLA-to-FrA axons was the strongest during safe periods in between conditioning pairings. Blocking BLA-to-FrA signaling specifically at the time of presentation of Gaussian noise (but not 8 kHz tone) as a safety signal impaired the formation of auditory fear memories. Taken together, our data reveal a circuit mechanism that facilitates the formation of fear traces in the FrA, thus providing a new framework for probing discriminative learning and related disorders.

scholarly journals The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning in mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mattia Aime ◽  
Elisabete Augusto ◽  
Vladimir Kouskoff ◽  
Tiago Campelo ◽  
Christelle Martin ◽  
...  
Keyword(s):  
Gaussian Noise ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Fear Learning ◽  
Association Cortex ◽  
Dependent Manner ◽  
Appropriate Behavior ◽  
Frontal Association Cortex ◽  
Time Of Presentation ◽  
New Framework

Survival depends on the ability of animals to select the appropriate behavior in response to threat and safety sensory cues. However, the synaptic and circuit mechanisms by which the brain learns to encode accurate predictors of threat and safety remain largely unexplored. Here, we show that frontal association cortex (FrA) pyramidal neurons of mice integrate auditory cues and basolateral amygdala (BLA) inputs non-linearly in a NMDAR-dependent manner. We found that the response of FrA pyramidal neurons was more pronounced to Gaussian noise than to pure frequency tones, and that the activation of BLA-to-FrA axons was the strongest in between conditioning pairings. Blocking BLA-to-FrA signaling specifically at the time of presentation of Gaussian noise (but not 8 kHz tone) between conditioning trials impaired the formation of auditory fear memories. Taken together, our data reveal a circuit mechanism that facilitates the formation of fear traces in the FrA, thus providing a new framework for probing discriminative learning and related disorders.

Muscarinic activation of a non-selective cationic conductance in pyramidal neurons in rat basolateral amygdala

Neuroscience ◽  
1999 ◽  
Vol 88 (1) ◽  
pp. 159-167 ◽  
Author(s):  
J Yajeya ◽  
A de la Fuente Juan ◽  
V.M Bajo ◽  
A.S Riolobos ◽  
M Heredia ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Pyramidal Neurons

Basolateral Amygdala Hyperexcitability is Associated With Precocious Developmental Emergence of Fear-Learning in Fragile X Syndrome

2021 ◽  
Author(s):  
Matthew N. Svalina ◽  
Christian Cea-Del Rio ◽  
Abigail Levy ◽  
Serapio M. Baca ◽  
E. Mae Guthman ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Basolateral Amygdala ◽  
Fragile X ◽  
Fear Learning

Metabotropic glutamate receptor agonist-induced hyperpolarizations in rat basolateral amygdala neurons: receptor characterization and ion channels

1996 ◽  
Vol 76 (5) ◽  
pp. 3059-3069 ◽  
Author(s):  
K. H. Holmes ◽  
N. B. Keele ◽  
V. L. Arvanov ◽  
P. Shinnick-Gallagher
Keyword(s):  
Dicarboxylic Acid ◽  
Glutamate Receptor ◽  
Basolateral Amygdala ◽  
Metabotropic Glutamate Receptor ◽  
Outward Current ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Metabotropic Glutamate ◽  
Outward Currents

1. Metabotropic glutamate receptor (mGluR)-agonist-induced hyperpolarizations and corresponding outward currents were analyzed in basolateral amygdala (BLA) neurons in rat brain slice preparations with current-clamp and single-electrode voltage-clamp recording to characterize the mGluR subtype(s) and the ion channel(s) mediating this response. 2. The mGluR agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induced a membrane hyperpolarization or outward current in BLA neurons in a concentration-dependent manner (median effective concentration = 34 microM; range = 10-200 microM); the 1S,3R-ACPD hyperpolarizations are recorded in 89% of neurons that accommodate or cease firing in response to a 400-ms depolarizing current injection (0.5 nA). 3. mGluR agonists elicited hyperpolarizations or outward currents in a concentration-dependent manner in the following rank order of potency: (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) > 1S,3R-ACPD > (s)-4-carboxyphenylglycine = (RS)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) > L-aminophosphonobutyric acid > (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid. In contrast, the mGluR agonists quisqualate and ibotenate induced only depolarizations in the presence of D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione in BLA neurons. 4. The 1S,3R-ACPD-induced outward current is mediated through a large-conductance calcium-dependent potassium (BK) conductance. The BK channel blockers iberiotoxin and charybdotoxin blocked the response, as did the potassium channel blockers tetraethylammonium and 4-aminopyridine; the small-conductance calcium-activated potassium channel blocker apamin did not affect the response. 5. The mGluR-agonist-induced hyperpolarization is blocked in amygdala slices from animals pretreated with pertussis toxin (PTX). 1S,3R-ACPD hyperpolarizations were recorded in neurons contralateral but not ipsilateral to the site of PTX injection. 6. The antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) reduced significantly the 1S,3R-ACPD-induced hyperpolarization. 7. In conclusion, the relative potency of L-CCG-I and 4C3HPG in evoking only hyperpolarizations (outward currents) in accommodating neurons, and the observation that MCPG (500 microM) reduces the hyperpolarization, suggest that a group-II-like mGluR underlies the hyperpolarizing response. The mGluR-induced response is sensitive to iberiotoxin and to pretreatment with PTX, suggesting activation of BK channels through a group II mGluR linked to a PTX-sensitive G protein in BLA neurons.

scholarly journals Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors

2018 ◽  
Vol 25 (11) ◽  
pp. 2832-2843 ◽  
Author(s):  
Amir Segev ◽  
Masaya Yanagi ◽  
Daniel Scott ◽  
Sarah A. Southcott ◽  
Jacob M. Lister ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Model Systems ◽  
Memory Processing ◽  
Hippocampal Subfields ◽  
Whole Cell Patch Clamp ◽  
Hippocampal Activity

Abstract Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.

The roles of basolateral amygdala parvalbumin neurons in fear learning

2021 ◽  
pp. JN-RM-2461-20
Author(s):  
Joanna Oi-Yue Yau ◽  
Chanchanok Chaichim ◽  
John M. Power ◽  
Gavan P. McNally
Keyword(s):  
Basolateral Amygdala ◽  
Fear Learning ◽  
Parvalbumin Neurons

scholarly journals Ontogenesis of Presynaptic GABAB Receptor-Mediated Inhibition in the CA3 Region of the Rat Hippocampus

1998 ◽  
Vol 79 (3) ◽  
pp. 1341-1348 ◽  
Author(s):  
Olivier Caillard ◽  
Heather A. McLean ◽  
Yehezkel Ben-Ari ◽  
Jean-Luc Gaïarsa
Keyword(s):  
Pyramidal Neurons ◽  
Gabab Receptor ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Rat Hippocampus ◽  
Dependent Manner ◽  
Paired Pulse ◽  
Ca3 Pyramidal Neurons ◽  
Paired Pulse Depression ◽  
Ca3 Region

Caillard, Olivier, Heather A. McLean, Yehezkel Ben-Ari, and Jean-Luc Gaı̈arsa. Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the rat hippocampus. J. Neurophysiol. 79: 1341–1348, 1998. γ-Aminobutyric acid-B(GABAB) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole cell recordings of CA3 pyramidal neurons were performed on hippocampal slices obtained from neonatal (5–7 day old) and adult (27–34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABAA postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and d(−)2-amino-5-phosphovaleric acid (d-AP5, 50 μM) with 2(triethylamino)- N-(2,6-dimethylphenyl) acetamine (QX314) filled electrodes. In adult CA3 pyramidal neurons, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1,500 ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blockedb y  P - 3 - a m i n o p r o p y l - P - d i e t h o x y m e t h y l  p h o s p h o r i c  a c i d(CGP35348, 0.5 mM), a selective GABAB receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABAB receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca2+ (4 mM)/low Mg2+ (0.3 mM) external solution revealed PPD in neonatal CA3 pyramidal neurons that was 1) partially prevented by CGP35348, 2) independent of the membrane holding potential of the recorded cell, and 3) not resulting from a change in the reversal potential of GABAA eIPSCs. In adults the GABA uptake blocker tiagabine (20 μM) increased the duration of eIPSCs and the magnitude of GABAB receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult and did not reveal a GABAB receptor-dependent PPD. These results demonstrate that although GABAB receptor-dependent and -independent mechanisms of presynaptic inhibition are present onGABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites.

scholarly journals Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex

2013 ◽  
Vol 110 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Jonathan Dilgen ◽  
Hugo A. Tejeda ◽  
Patricio O'Donnell
Keyword(s):  
Prefrontal Cortex ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Reversal Potential ◽  
Intracellular Recordings ◽  
Action Potential Firing ◽  
Gaba A ◽  
Potential Firing ◽  
Feedforward Inhibition

Although interactions between the amygdala and prefrontal cortex (PFC) are critical for emotional guidance of behavior, the manner in which amygdala affects PFC function is not clear. Whereas basolateral amygdala (BLA) output neurons exhibit many characteristics associated with excitatory neurotransmission, BLA stimulation typically inhibits PFC cell firing. This apparent discrepancy could be explained if local PFC inhibitory interneurons were activated by BLA inputs. Here, we used in vivo juxtacellular and intracellular recordings in anesthetized rats to investigate whether BLA inputs evoke feedforward inhibition in the PFC. Juxtacellular recordings revealed that BLA stimulation evoked action potentials in PFC interneurons and silenced most pyramidal neurons. Intracellular recordings from PFC pyramidal neurons showed depolarizing postsynaptic potentials, with multiple components evoked by BLA stimulation. These responses exhibited a relatively negative reversal potential (Erev), suggesting the contribution of a chloride component. Intracellular administration or pressure ejection of the GABA-A antagonist picrotoxin resulted in action-potential firing during the BLA-evoked response, which had a more depolarized Erev. These results suggest that BLA stimulation engages a powerful inhibitory mechanism within the PFC mediated by local circuit interneurons.

Acquisition of Fear and Extinction in Lateral Amygdala: A Modeling Study

2010 ◽  
Author(s):  
Sandeep Pendyam ◽  
Dongbeom Kim ◽  
Gregory J. Quirk ◽  
Satish S. Nair
Keyword(s):  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Fear Learning ◽  
Cell Populations ◽  
Storage Site ◽  
Somatosensory Information ◽  
Cortical Inputs ◽  
Lateral Nucleus ◽  
And Storage

The lateral nucleus of amygdala (LA) is known to be a critical storage site for conditioned fear memory. Synaptic plasticity at auditory inputs to the dorsal LA (LAd) is critical for the formation and storage of auditory fear memories. Recent evidence suggests that two different cell populations (transient- and long-term plastic cells) are present in LAd and are responsible for fear learning. However, the mechanisms involved in the formation and storage of fear are not well understood. As an extension of previous work, a biologically realistic computational model of the LAd circuitry is developed to investigate these mechanisms. The network model consists of 52 LA pyramidal neurons and 13 interneurons. Auditory and somatosensory information reaches LA from both thalamic and cortical inputs. The model replicated the tone responses observed in the two LAd cell populations during conditioning and extinction. The model provides insights into the role of thalamic and cortical inputs in fear memory formation and storage.

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