The neural correlates of justified and unjustified killing: An fMRI study

Despite moral prohibitions on hurting other humans, some social contexts allow for harmful actions such as the killing of others. One example is warfare, where killing enemy soldiers is seen as morally justified. Yet, the neural underpinnings distinguishing between justified and unjustified killing are largely unknown. To improve understanding of the neural processes involved in justified and unjustified killing, participants had to imagine being the perpetrator whilst watching “first-person perspective” animated videos where they shot enemy soldiers (‘justified violence’) and innocent civilians (‘unjustified violence’). When participants imagined themselves shooting civilians compared to soldiers, greater activation was found in the lateral orbitofrontal cortex (OFC). Regression analysis revealed that the more guilt participants felt about shooting civilians, the greater the response in the lateral OFC. Effective connectivity analyses further revealed an increased coupling between lateral OFC and the tempoparietal junction (TPJ) when shooting civilians. The results show that the neural mechanisms typically implicated with harming others, such as the OFC, become less active when the violence against a particular group is seen as justified. This study therefore provides unique insight into how normal individuals can become aggressors in specific situations.

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...

Biophysical correlates of intrinsic and stress-induced morphological variability in lateral amygdaloid neurons: A computational study

Morphological and physiological characteristics of neurons located in the dorsolateral and two ventral subdivisions of the lateral amygdala (LA) have been compared in order to differentiate their roles in the formation and storage of fear memories (Alphs et al, SfN abs 623.1, 2003). Briefly, in these populations, significant differences are observed in input resistance, membrane time constant, firing frequency, dendritic tortuosity, numbers of primary dendrites, dendritic segments and dendritic nodes...

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...

Acute restraint stress alters subsequent auditory fear conditioning in the rat

The neural basis of Pavlovian fear conditioning is well understood and depends upon neural processes within the amygdala. Stress is known to play a role in the modulation of fear-related behavior, including Pavlovian fear conditioning. Chronic restraint stress has been shown to enhance fear conditioning to discrete and contextual stimuli; however, the time course and extent of restraint that is essential for this modulation of fear learning remains unclear. Thus, we tested the extent to which a single exposure to 1 hr of restraint would alter subsequent auditory fear conditioning in rats.

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.

GABAergic inhibition in the fear conditioning circuit of the lateral amygdala is potentiated by dopamine D1 agonists

Auditory fear conditioning is dependent on auditory signaling from the medial geniculate (MGm) and the auditory cortex (TE3) to principal neurons of the lateral amygdala (LA). Local circuit GABAergic interneurons are known to inhibit LA principal neurons via fast and slow IPSP's. Stimulation of MGm and TE3 produces excitatory post-synaptic potentials in both LA principal and interneurons, followed by inhibitory post-synaptic potentials. Manipulations of D1 receptors in the lateral and basal amygdala modulate the retrieval of learned association between an auditory CS and foot shock. Here we examined the effects of D1 agonists on GABAergic IPSP's evoked by stimulation of MGm and TE3 afferents in vitro. Whole cell patch recordings were made from principal neurons of the LA, at room temperature, in coronal brain slices using standard methods. Stimulating electrodes were placed on the fiber tracts medial to the LA and at the external capsule/layer VI border dorsal to the LA to activate (0.1-0.2mA) MGm and TE3 afferents respectively. Neurons were held at -55.0 mV by positive current injection to measure the amplitude of the fast IPSP. Changes in input resistance and membrane potential were measured in the absence of current injection. Stimulation of MGm or TE3 afferents produced EPSP's in the majority of principal neurons and in some an EPSP/IPSP sequence. Stimulation of MGm afferents produced IPSP's with amplitudes of -2.30 ± 0.53 mV and stimulation of TE3 afferents produced IPSP's with amplitudes of -1.98 ± 1.26 mV. Bath application of 20μM SKF38393 increased IPSP amplitudes to -5.94 ± 1.62 mV (MGm, n=3) and-5.46 ± 0.31 mV (TE3, n=3). Maximal effect occurred <10mins. A small increase in resting membrane potential and decrease in input resistance were observed. These data suggest that DA modulates both the auditory thalamic and auditory cortical inputs to the LA fear conditioning circuit via local GABAergic circuits. Supported by NIMH Grants 00956, 46516, and 58911.

Differing phagocytic capacities of accessory and main olfactory ensheathing cells and the implication for olfactory glia transplantation therapies

The rodent olfactory systems comprise the main olfactory system for the detection of odours and the accessory olfactory system which detects pheromones. In both systems, olfactory axon fascicles are ensheathed by olfactory glia, termed olfactory ensheathing cells (OECs), which are crucial for the growth and maintenance of the olfactory nerve. The growth-promoting and phagocytic characteristics of OECs make them potential candidates for neural repair therapies such as transplantation to repair the injured spinal cord. However, transplanting mixed populations of glia with unknown properties may lead to variations in outcomes for neural repair. As the phagocytic capacity of the accessory OECs has not yet been determined, we compared the phagocytic capacity of accessory and main OECs in vivo and in vitro. In normal healthy animals, the accessory OECs accumulated considerably less axon debris than main OECs in vivo. Analysis of freshly dissected OECs showed that accessory OECs contained 20% less fluorescent axon debris than main OECs. However, when assayed in vitro with exogenous axon debris added to the culture, the accessory OECs phagocytosed almost 20% more debris than main OECs. After surgical removal of one olfactory bulb which induced the degradation of main and accessory olfactory sensory axons, the accessory OECs responded by phagocytosing the axon debris. We conclude that while accessory OECs have the capacity to phagocytose axon debris, there are distinct differences in their phagocytic capacity compared to main OECs. These distinct differences may be of importance when preparing OECs for neural transplant repair therapies.