Fear and the amygdala

What is fear? Why are we sometimes afraid? Can fear be inhibited? What produces fear – the brain or the heart?

It is definitely the brain! More exactly, something in the brain – a tiny, almond-shaped structure, which sits anteriorly to the hippocampus, called the amygdala. This small part of our brain is to blame for  the perception of fearful stimuli and the physiological responses (increased heart rate, electrodermal responses etc.) to fearful stimuli.

As part of the FEAR system, the amygdala connects to the medial hypothalamus and the dorsal periaqueductal grey matter (in the midbrain), which is important in pain modulation in the dorsal horn of the spinal cord, as well as to sensory and association cortices. The lateral nucleus of the amygdala receives inputs from different brain regions, thus allowing the formation of associations, required for aversive conditioning. Following the processing in the lateral nucleus, information about the stimulus is, then, projected to the central nucleus of the amygdala, where an appropriate response to the stimuli is initiated, provided that the stimuli are detected as threatening or potentially dangerous.

The amygdala is involved in emotional learning and memory, modulating implicit learning, explicit memory, attention, social responses, emotion inhibition and vigilance.

You can find the article on memory here, to brush up a bit.

  • Implicit memory is a type of learning, which cannot be voluntarily reported or remembered. It includes the memories for skills and habits, for procedural knowledge, grammar and languages, priming, simple forms of associative learning and classical conditioning. The latter is particularly important for fear. It involved a conditioned stimulus (CS) and an unconditioned, painful/fearful stimulus (US), with US preceding CS and determining a fearful response to CS. This type of fear learning is adaptive and is known as sensitisation or acquisition.

There are two different pathways in the amygdala, important for fear conditioning. The “low road” pathway: sensory information projects to the thalamus, which directly communicates with the amygdala; this pathway is fast, modulating rapid responses of the amygdala to different types of fearful stimuli. The “high road” pathway is an indirect pathway: sensory information projects to the thalamus and from there, it is conveyed to the sensory cortex for a finer analysis; the sensory cortex, then, communicates the processed information to the amygdala. This pathway ensures that the sensory stimulus is the conditioned stimulus. So the responses of amygdala to threatening stimuli are both rapid and sure.

  • Explicit memory refers to the memory of facts and events; in the case of fear is means the processing and retention for a long time, of emotional events and information. For this type of fear learning, the amygdala interacts with the hippocampus. There is a distinction between the formation of memory for aversive experience (fear conditioning), which is based on previous experience, and explicit learning (in the hippocampus), which involves learning and remembering aversive properties of different threatening stimuli. The memory in the hippocampus is enhanced by arousal produced in the amygdala. The activation of the amygdala can make different cortical areas, not just the hippocampus, more receptive to stimuli that are adaptively important, thus ensuring that unattended, but important stimuli gain access to consciousness.
  • Social responses involve the ability to recognise a stimulus as good, bad, neutral or arousing. This ability, however, does not depend on the amygdala. There is one exception here, otherwise we wouldn’t be talking about it in the context of fear mediated by amygdala – fearful facial expressions. According to Darwin, social species, like humans, use facial expressions to detect internal emotional states of other members of the group. This function, mediated by the amygdala, is crucial in the emotional regulation of human social behaviour. Damage to amygdala has been demonstrated to result in impairment of the patient to identify fearful faces correctly and, therefore, react to them, accordingly. It should also be noted there is no need for the subject’s awareness of the fearful stimulus, for the amygdala to respond. In other words, when a fearful facial expression is presented subliminally, the amygdala will still show activation.
  • Inhibition of fear – it is actually very difficult to escape your own fears, as fear proves to be resistant to voluntary control. However, there is a process called extinction, a method of classical conditioning, where a CS previously associated with an aversive US in presented alone for a number of times, until the CS no longer signals the fearful stimulus. If the US is presented again, after the passage of time, it will evoke fear responses, but in different brain areas. So, the learned fear has been retained in memory, but extinction learning eliminates the response to fear. This mechanism of extinction relies on the activity of NMDA glutamate (excitatory) receptors in the amygdala. When these receptors are blocked, extinction is inhibited (so you will react to fearful stimuli) and when they are active, extinction is augmented (you no longer respond to aversive stimuli).
  • Vigilance – the amygdala is not necessary for the conscious experience of emotional states, but it plays a major role in increasing the vigilance of cortical response systems to emotional stimuli.

Memories about fearful events, just like other types of long-term memory, become permanent through a process of gene expression and novel protein synthesis, which is known as consolidation. Upon retrieval, the memories become susceptible to change and alteration, before they are reconsolidated, which involves additional protein synthesis.

The fact that humans (and probably other animals as well, I am sure, although not widely proven) have the ability to distinguish between emotional information and unemotional information is regarded as an evolutionary advantage. Emotional stimuli signal dangers and the ability to detect and appropriately react to them increases the chance of survival. However, exacerbated fear is detrimental to the individual who experiences it and is a sign of pathology. For instance, in atypical monopolar depression, which includes anxiety as one of the main symptoms, the amygdala is overactive and it determined lowering the threshold for emotional activation and abnormal reactions to stressful stimuli. A similar pattern can be seen as a result of partial chronic sleep deprivation or complete acute sleep deprivation.

References

 Beatty, 2001. The Human Brain – Essentials of Behavioural Neuroscience, Sage Publications Ltd., pg. 293-296

Bernard et al., 2007. Cognition, Brain and Consciousness – Introduction to Cognitive Neuroscience. 1st edition. Elsevier Ltd., pg. 373-383

Gazzaniga et al., 2002. Cognitive Neuroscience – The Biology of Mind. 2nd edition. W.W Norton & Company, Inc., pg. 553-572

Image by  Saya Lohovska. You can find her arts page here.

Even flies sleep and learn

Sleep is a fascinating process that allows most of the creatures on Earth to function at their normal capacity and survive the environmental challenges. Recent theories support the idea that one of the main functions of sleep is not energy conservation or tissue restoration, as previously thought, but actually, enhancement of brain function. Sleep appears to be involved in consolidation of memories and improvement of learning. As you probably remember from the previous article, there are essentially to phases of sleep: REM and non-REM. The latter has been shown to be involved in consolidation of both declarative and non-declarative memories, whereas REM sleep is believed to enhance the formation of procedural and emotional (non-declarative) memories.

If you’ve ever wondered whether insects can sleep or not, the answer is yes. Several studies in Drosophila melanogaster , the fruit fly famous for Morgan’s discoveries of chromosomal inheritance, proved these flies have periods of ‘rest’. During rest , Drosophila stops moving and becomes more difficult to be aroused, which resembles what we understand by ‘sleep’. Moreover, it appears that these flies can form short-term and long-term memories, especially revealed by studies of olfactory associative conditioning. Surprising, isn’t it? Even though it is known that insects have brains, they seem too primitive, at a first glance, for complex cognitive functions such as memory and learning. Well, it’s obvious that insects are much smarter than we thought.

What’s more stunning is that, in Drosophila, just as in humans, sleep has evident effects on long term memory formation and sleep deprivation can dramatically affect this function. According to several studies, sleep homeostasis positively influences learning. During non-REM sleep, the brain shows slow oscillatory activity, which is characterised by waves of action potentials with low frequency and high amplitude. These slow waves are controlled by homeostatic processes and increase after learning tasks. Hence, sleep, which induces slow wave activity, plays a very important role in enhancing learning performances.

The homeostatic control of sleep has been somewhat elucidated by studies in our old friend, Drosophila. Organisms need not only a circadian clock (which sets a day-night rhythm, synchronising the body with the environment), but also a homeostatic system, which regulates sleep according to prior wakefulness. Just like in the circadian system, the homeostatic system seems to be genetically regulated and, eventually, resulting from neuronal activity.

Specialised sleep-promoter neurones in Drosophila, called the dorsal fan-shaped body (FB) neurones, become excited when the organism is sleep-deprived and fire action potentials (which can be surprising, given that non-REM sleep triggers reduced brain activity). It is not exactly known how the nervous system can sense lack of sleep, but it is believed that substances such as adenosine and unfolded proteins, released after prolonged wakefulness, are potential signals. Thus, after detecting too much wakefulness, dorsal FB neurones become excited and promote sleep. The gene that controls the function of the dorsal FB neurones is the crossveinless-c (cv-c) gene, which encodes for a protein that regulates different ion channels (especially potassium channels), leading to changes in electrical conductance and the excitability of the sleep-promoter neurones.

 Just to give some more information and (possibly) complicate things a bit more, another link between sleep and long term memory is represented by the notch receptors, which have been found to be involved in the restoration of long term memory formation after sleep deprivation. Their main function is to influence the development of the nervous system in the embryo, but they also play a role in memory formation.

 As you have probably figured out by now, it is quite hard to have a complete picture of what sleep is about and how it can influence memory and learning. However, scientists are doing their best to shed some light on these wonderful phenomena. And before you close this page, don’t forget an important point: even something small like the fruit fly is able to sleep and learn!

I’d like to thank my friends Parnian Doostdar and Lee Chi Yu for sending me most of the materials I used for this article.

For further information:

Article 

Ackermann, S., Rasch, B., 2014. Differential effects of non-REM and REM on memory consolidation, Current neurology and neuroscience reports, vol. 14, p. 430

Donlea, J. M., Pimentel, D., Miesenbock, G., 2014. Neuronal machinery of sleep homeostasis in Drosophila. Neuron, vol. 81, pp. 860-872

Huber, R., Ghilardi, M. F., Massimini, M., Tononi, G., 2004. Local sleep and learning. Nature, vol. 430, pp. 78-81