Systematic constellations of neurons are activated in lateral amygdala following Pavlovian fear conditioning

How memory is organized within neural networks is a fundamental question in neuroscience. We used Pavlovian fear conditioning to study the discrete organization patterns of neurons activated in an associative memory paradigm. In Pavlovian fear conditioning a neutral stimulus, such as an auditory tone, is temporally paired with an aversive unconditioned stimulus (US), such as a foot shock...

Afferent specific regulation of cortical and subcortical synaptic input to the lateral amygdala by norepinephrine

The lateral amygdala (LA) has been extensively implicated in the neurobiology of conditioned fear paradigms. Norepinepherine (NE), especially its beta receptors, has been implicated in consolidation, reconsolidation and extinction of fear memories, and has been proposed as a potential treatment for PTSD (Berlau and McGaugh, NLM, 2006; Debiec and LeDoux, N, 2005)...

A recurrent network in the lateral amygdala: A mechanism for temporal coincidence detection

The dorsal lateral amygdala (LAd) is a vital nucleus for the formation of associations between aversive unconditioned stimuli (US) and neutral stimuli, such as auditory tones, which can become conditioned (CS) to the US through temporal pairing. Important aspects of CS-US associations are believed to occur within the LAd, however relatively little is known about the temporal behavior of local LAd networks. Information about the CS and US enters the LA via a rapid and direct thalamic input and a longer latency cortical path...

GABAA and NMDA receptors contribute to synaptic integration in lateral amygdala neurons

In classical fear conditioning a neutral conditioned stimulus (CS), is paired with an aversive unconditioned stimulus (US). The CS thereby acquires the capacity to elicit a fear response. This type of associative learning is thought to require co-activation of principal neurons in the lateral nucleus of the amygdala (LA) by two sets of synaptic inputs...

Polysynaptic potentials within the lateral amygdala networks as indicators of reverberatory activity

Synaptic plasticity in the lateral amygdala (LA) may underlie auditory fear conditioning. Hebb postulated that sustained activity in reverberating cellular ensembles can facilitate temporal coincidence detection. Our anatomical data show that LA neurons have extensive local axon collaterals that are topographically organized and that could provide the anatomical basis for reverberatory activity...

Amygdala-dependent learning increases the number of spinophilin-immunoreactive dendritic spines in the lateral amygdala

During Pavlovian auditory fear conditioning a previously neutral auditory stimulus (CS) gains emotional significance through pairing with a noxious unconditioned stimulus (US). These associations are believed to be formed by way of plasticity at auditory input synapses on principal neurons in the lateral nucleus of the amygdala (LA). One proposed form of cellular plasticity involves structural changes in the number and morphology of dendritic spines...

Differences in intrinsic properties of dorsally and ventrally located lateral amygdala neurons of the rat

During Pavlovian auditory fear conditioning a previously neutral auditory stimulus (CS) gains emotional significance through pairing with a noxious unconditioned stimulus (US). These associations are believed to be formed by way of plasticity at auditory input synapses on principal neurons of the lateral nucleus of the amygdala (LA). While the LA has been implicated as a key brain structure for fear learning, how its network of cellular components performs these operations is not yet known...

GABAa receptors contribute to synaptic integration in lateral amygdala neurons

In classical fear conditioning a neutral conditioned stimulus (CS) such as a tone, is paired with an aversive unconditioned stimulus (US) such as a shock. The CS thereby acquires the capacity to elicit a fear response. This type of associative learning is thought to require co-activation of principle neurons in the lateral nucleus of the amygdala (LA) by two sets of synaptic inputs, a weak CS and a strong US...

Propagating excitatory potentials within the fear conditioning circuit of the lateral amygdala

In the Hebbian postulate, transiently reverberating cellular ensembles can sustain activity to facilitate temporal coincidence detection. Auditory fear conditioning is believed to be formed in the lateral amygdala (LA), by way of plasticity at auditory input synapses on principal neurons. To evaluate the contribution of LA cellular ensembles in the formation of conditioned fear memories, we investigated the LA micro-circuitry by electrophysiological and anatomical approaches. Polysynaptic field potentials evoked in the LA by stimulation of auditory thalamus(MGm/PIN) or auditory cortical (TE3) afferents were analyzed in vitro and in vivo. In vivo, two potentials were identified following stimulation of either pathway. In vitro, these multiple potentials were revealed by adding 75uM Picrotoxin or 30uM Bicuculine, with the first potential peaking at 15-20 ms, followed by two additional potentials at 20 – 25 and 30 – 35 ms, respectively. These data show single stimulation events can result in multiple synchronized excitatory events within the lateral amygdala. In order to determine underlying mechanisms of auditory signal propagation, LA principal neuron axon collateral trajectory patterns and morphology were analyzed. Neurons were found to have local axon collaterals that are topographically organized. Each axon collateral within the LA totaled 14.1 ± 2.73mm, had 29.8 ± 9.1 branch points and 1870.8 ± 1035 boutons (n=9). Electrophysiological and anatomical data show that a network of extensive axon collaterals within the LA may facilitate preservation of auditory afferent signals.

Quantification of the total neuronal structure of the fear conditioning circuit of the lateral amygdala of the rat

During Pavlovian auditory fear conditioning a previously neutral auditory stimulus (CS) gains emotional significance through pairing with a noxious unconditioned stimulus (US). These associations are believed to be formed by way of plasticity at auditory input synapses on principal neurons in the lateral nucleus of the amygdala (LA). In order to begin to understand how fear memories are stored and processed by synaptic changes in the LA, we have quantified both the entire neural number and the sub-cellular structure of LA principal neurons.We first used stereological cell counting methods on Gimsa or GABA immunostained rat brain. We identified 60,322+/-1408 neurons in the LA unilaterally (n=7). Of these 16,917+/-471 were GABA positive. The intercalated nuclei were excluded from the counts and thus GABA cells are believed to represent GABAergic interneurons. The sub-nuclei of the LA were also independently counted. We then quantified the morphometric properties of in vitro electrophysiologically identified principal neurons of the LA, corrected for shrinkage in xyz planes. The total dendritic length was 9.97+/-2.57mm, with 21+/-4 nodes (n=6). Dendritic spine density was 0.19+/-0.03 spines/um (n=6). Intra-LA axon collaterals had a bouton density of 0.1+/-0.02 boutons/um (n=5). These data begin to reveal the finite cellular and sub-cellular processing capacity of the lateral amygdala, and should facilitate efforts to understand mechanisms of plasticity in LA.