scholarly journals Morphology, PKCδ expression, and synaptic responsiveness of different types of rat central lateral amygdala neurons

2012 ◽  
Vol 108 (12) ◽  
pp. 3196-3205 ◽  
Author(s):  
Taiju Amano ◽  
Alon Amir ◽  
Sonal Goswami ◽  
Denis Paré

Recent findings implicate the central lateral amygdala (CeL) in conditioned fear. Indeed, CeL contains neurons exhibiting positive (CeL-On) or negative (CeL-Off) responses to fear-inducing conditioned stimuli (CSs). In mice, these cells differ in their expression of protein kinase Cδ (PKCδ) and physiological properties. CeL-Off cells are PKCδ+ and late firing (LF), whereas CeL-On cells are PKCδ− and express a regular-spiking (RS) or low-threshold bursting (LTB) phenotype. However, the scarcity of LF cells in rats raises questions about the correspondence between the organization of CeL in mice and rats. Therefore, we studied the PKCδ expression, morphological properties, synaptic responsiveness, and fear conditioning-induced plasticity of rat CeL neurons. No PKCδ+ LF cells were encountered, but ≈20–25% of RS and LTB neurons were PKCδ+. Compared with RS neurons, a higher proportion of LTB cells projected to central medial amygdala (CeM) and they had fewer primary dendritic branches, yet the amplitude of excitatory postsynaptic potentials (EPSPs) evoked by lateral amygdala (LA) stimulation was similar in RS and LTB cells. In contrast, LA-evoked inhibitory postsynaptic potentials (IPSPs) had a higher amplitude in LTB than RS neurons. Finally, fear conditioning did not induce plasticity at LA inputs to RS or LTB neurons. These findings point to major species differences in the organization of CeL. Since rat LTB cells are subjected to stronger feedforward inhibition, they are more likely to exhibit inhibitory CS responses than RS cells. This is expected to cause a disinhibition of CeM fear output neurons and therefore an increase in fear expression.

2013 ◽  
Vol 110 (4) ◽  
pp. 844-861 ◽  
Author(s):  
Sandeep Pendyam ◽  
Christian Bravo-Rivera ◽  
Anthony Burgos-Robles ◽  
Francisco Sotres-Bayon ◽  
Gregory J. Quirk ◽  
...  

The acquisition and expression of conditioned fear depends on prefrontal-amygdala circuits. Auditory fear conditioning increases the tone responses of lateral amygdala neurons, but the increase is transient, lasting only a few hundred milliseconds after tone onset. It was recently reported that that the prelimbic (PL) prefrontal cortex transforms transient lateral amygdala input into a sustained PL output, which could drive fear responses via projections to the lateral division of basal amygdala (BL). To explore the possible mechanisms involved in this transformation, we developed a large-scale biophysical model of the BL-PL network, consisting of 850 conductance-based Hodgkin-Huxley-type cells, calcium-based learning, and neuromodulator effects. The model predicts that sustained firing in PL can be derived from BL-induced release of dopamine and norepinephrine that is maintained by PL-BL interconnections. These predictions were confirmed with physiological recordings from PL neurons during fear conditioning with the selective β-blocker propranolol and by inactivation of BL with muscimol. Our model suggests that PL has a higher bandwidth than BL, due to PL's decreased internal inhibition and lower spiking thresholds. It also suggests that variations in specific microcircuits in the PL-BL interconnection can have a significant impact on the expression of fear, possibly explaining individual variability in fear responses. The human homolog of PL could thus be an effective target for anxiety disorders.


2009 ◽  
Vol 101 (3) ◽  
pp. 1629-1646 ◽  
Author(s):  
Guoshi Li ◽  
Satish S. Nair ◽  
Gregory J. Quirk

The basolateral amygdala plays an important role in the acquisition and expression of both fear conditioning and fear extinction. To understand how a single structure could encode these “opposite” memories, we developed a biophysical network model of the lateral amygdala (LA) neurons during auditory fear conditioning and extinction. Membrane channel properties were selected to match waveforms and firing properties of pyramidal cells and interneurons in LA, from published in vitro studies. Hebbian plasticity was implemented in excitatory AMPA and inhibitory GABAA receptor-mediated synapses to model learning. The occurrence of synaptic potentiation versus depression was determined by intracellular calcium levels, according to the calcium control hypothesis. The model was able to replicate conditioning- and extinction-induced changes in tone responses of LA neurons in behaving rats. Our main finding is that LA activity during both acquisition and extinction can be controlled by a balance between pyramidal cell and interneuron activations. Extinction training depressed conditioned synapses and also potentiated local interneurons, thereby inhibiting the responses of pyramidal cells to auditory input. Both long-term depression and potentiation of inhibition were required to initiate and maintain extinction. The model provides insights into the sites of plasticity in conditioning and extinction, the mechanism of spontaneous recovery, and the role of amygdala NMDA receptors in extinction learning.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhenfu Wen ◽  
Marie-France Marin ◽  
Jennifer Urbano Blackford ◽  
Zhe Sage Chen ◽  
Mohammed R. Milad

AbstractTranslational models of fear conditioning and extinction have elucidated a core neural network involved in the learning, consolidation, and expression of conditioned fear and its extinction. Anxious or trauma-exposed brains are characterized by dysregulated neural activations within regions of this fear network. In this study, we examined how the functional MRI activations of 10 brain regions commonly activated during fear conditioning and extinction might distinguish anxious or trauma-exposed brains from controls. To achieve this, activations during four phases of a fear conditioning and extinction paradigm in 304 participants with or without a psychiatric diagnosis were studied. By training convolutional neural networks (CNNs) using task-specific brain activations, we reliably distinguished the anxious and trauma-exposed brains from controls. The performance of models decreased significantly when we trained our CNN using activations from task-irrelevant brain regions or from a brain network that is irrelevant to fear. Our results suggest that neuroimaging data analytics of task-induced brain activations within the fear network might provide novel prospects for development of brain-based psychiatric diagnosis.


Author(s):  
Julia Reinhard ◽  
Anna Slyschak ◽  
Miriam A. Schiele ◽  
Marta Andreatta ◽  
Katharina Kneer ◽  
...  

AbstractThe aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.


2002 ◽  
Vol 87 (2) ◽  
pp. 1057-1067 ◽  
Author(s):  
Akira Haji ◽  
Mari Okazaki ◽  
Hiromi Yamazaki ◽  
Ryuji Takeda

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-d-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Anwesha Banerjee ◽  
Jonathan A. Luong ◽  
Anthony Ho ◽  
Aeshah O. Saib ◽  
Jonathan E. Ploski

1983 ◽  
Vol 218 (1210) ◽  
pp. 95-110 ◽  

(i) Following previous work on the morphological and physiological properties of the two distal joints (J2, J3) of the atenna of the rock lobster Palinurus vulgaris , the mechanical, muscular and proprioceptive organization of the two proximal joints between the antennal segments S1 and S2 (J1) and between S1 and the cephalothorax (J0) have now been studied. (ii) Articulated by two classical condyles, J1 moves in a mediolateral plane. One external rotator muscle (ER) and three internal rotator muscles (IR1, IR2, IR3) subserve its movements. J0 is articulated by two different systems: a classical ventrolateral condyle and a complex sliding system constituted by special cuticular structures on the dorsomedial side of the S1 segment and on the rostrum between the two antennae. J0 moves in the dorsoventral plane by means of a levator muscle (Lm) and a depressor muscle (Dm). A third muscle, the lateral tractor muscle (LTm), associated with J0 and lying obliquely across S1, may modulate the level of friction between the S1 segment and the rostrum. (iii) Proprioception in J1 is achieved by a muscle receptor organ AMCO-J1 (antennal myochordotonal organ for the J1 joint) associating a small accessory muscle (S1.am) located in the proximal part of the S1 segment and a chordotonal organ inserted proximally on the S1.am muscle and distally on the S2 segment. J0 proprioception is ensured by a simple chordotonal organ (CO-J0) located in the anterior part of the cephalothorax. (iv) The S1.am muscle is innervated by three motoneurons characterized by their very small diameters and inducing respectively tonic excitatory postsynaptic potentials, phasic excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Anatomical and physiological observations suggest functional correlation between S1.am and IR1 motor innervation. (v) Mechanical and muscular organization of J0 and J1 are compared with that of the other joints of the antenna. The properties of the AMCO-J1 proprioceptor are discussed in relation to the other muscle receptor organs described in crustaceans.


2001 ◽  
Vol 85 (2) ◽  
pp. 714-723 ◽  
Author(s):  
E.S.L. Faber ◽  
R. J. Callister ◽  
P. Sah

In this study, we characterize the electrophysiological and morphological properties of spiny principal neurons in the rat lateral amygdala using whole cell recordings in acute brain slices. These neurons exhibited a range of firing properties in response to prolonged current injection. Responses varied from cells that showed full spike frequency adaptation, spiking three to five times, to those that showed no adaptation. The differences in firing patterns were largely explained by the amplitude of the afterhyperpolarization (AHP) that followed spike trains. Cells that showed full spike frequency adaptation had large amplitude slow AHPs, whereas cells that discharged tonically had slow AHPs of much smaller amplitude. During spike trains, all cells showed a similar broadening of their action potentials. Biocytin-filled neurons showed a range of pyramidal-like morphologies, differed in dendritic complexity, had spiny dendrites, and differed in the degree to which they clearly exhibited apical versus basal dendrites. Quantitative analysis revealed no association between cell morphology and firing properties. We conclude that the discharge properties of neurons in the lateral nucleus, in response to somatic current injections, are determined by the differential distribution of ionic conductances rather than through mechanisms that rely on cell morphology.


10.1038/89465 ◽  
2001 ◽  
Vol 4 (7) ◽  
pp. 687-688 ◽  
Author(s):  
Elizabeth P. Bauer ◽  
Joseph E. LeDoux ◽  
Karim Nader

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