Amygdala
The amygdala is a paired nuclear complex present in the cerebral hemispheres of vertebrates. It is considered part of the limbic system. In primates, it is located medially within the temporal lobes. It consists of many nuclei, each made up of further subnuclei. The subdivision most commonly made is into the basolateral, central, cortical, and medial nuclei together with the intercalated cell clusters. The amygdala has a primary role in the processing of memory, decision-making, and emotional responses. The amygdala was first identified and named by Karl Friedrich Burdach in 1822.
Structure
Thirteen nuclei have been identified, each with its own subdivisions and distinct connections to the rest of the brain. The chief nuclei are the basolateral complex, the central nucleus, the cortical nucleus, the medial nucleus, and the intercalated cell clusters. The cortical and medial nuclei connect with the olfactory system and hypothalamus. The central nucleus has extensive projections to the brainstem.The basolateral complex can be further subdivided into the lateral, the basal, and the accessory basal nuclei. It has extensive connections with higher-order cortical areas in the prefrontal, temporal, insular cortices, and the hippocampus. The basolateral complex is surrounded by the intercalated cell net that is inhibitory and projects to a broad variety of areas in the basal forebrain, hypothalamus, and the amygdala.
The primate amygdala contains about 32 different types of neuron.
Hemispheric specializations
The right and left portions of the amygdala have independent memory systems, but work together to store, encode, and interpret emotion.The right hemisphere of the amygdala is associated with negative emotion. It plays a role in the expression of fear and in the processing of fear-inducing stimuli. Fear conditioning, which occurs when a neutral stimulus acquires aversive properties, occurs within the right hemisphere. When an individual is presented with a conditioned, aversive stimulus, it is processed within the right amygdala, producing an unpleasant or fearful response. This emotional response conditions the individual to avoid fear-inducing stimuli and more importantly, to assess threats in the environment.
The right hemisphere is also linked to declarative memory, which consists of facts and information from previously experienced events and must be consciously recalled. It also plays a significant role in the retention of episodic memory. Episodic memory consists of the autobiographical aspects of memory, permitting recall of emotional and sensory experience of an event. This type of memory does not require conscious recall. The right amygdala plays a role in the association of time and places with emotional properties.
In one study, electrical stimulations of the right amygdala induced negative emotions, especially fear and sadness. In contrast, stimulation of the left amygdala was able to induce either pleasant or unpleasant emotions. Other evidence suggests that the left amygdala plays a role in the brain's reward system.
Development and sex distinction
The amygdala is one of the best-understood brain regions with regard to differences between the sexes. The amygdala is larger in males than females, in children aged 7 to 11, adult humans, and adult rats.There is considerable growth within the first few years of structural development in both male and female amygdalae. Within this early period, female limbic structures grow at a more rapid pace than the male ones. Amongst female subjects, the amygdala reaches its full growth potential approximately 1.5 years before the peak of male development. The structural development of the male amygdala occurs over a longer period than in women. Because of the early development of female amygdalae, they reach their growth potential sooner than males, whose amygdalae continue to develop. The larger relative size of the male amygdala may be attributed to this extended developmental period.
Hormonal factors may contribute to these sex-specific developmental differences. The amygdala is rich in androgen receptors—nuclear receptors that bind to testosterone. Androgen receptors play a role in the DNA binding that regulates gene expression. Though testosterone is present within the female hormonal systems, women have lower levels of testosterone than men. The abundance of testosterone in the male hormonal system may contribute to development. In addition, the grey matter volume on the amygdala is predicted by testosterone levels, which may also contribute to the increased mass of the male amygdala.
There are observable developmental differences between the right and left amygdala. The left amygdala reaches its developmental peak approximately 1.5–2 years prior to the right amygdala. Despite the early growth of the left amygdala, the right increases in volume for a longer period of time. The right amygdala is associated with response to fearful stimuli as well as face recognition. For the left amygdala, it is inferred that the early development of it functions to provide infants the ability to detect danger due to its reported responds predominantly to fearful events and faces. In childhood, the amygdala is found to react differently to same-sex versus opposite-sex individuals. This reactivity decreases until a person enters adolescence, where it increases dramatically at puberty.
Other functional and structural differences between male and female amygdalae have been observed. Subjects' amygdala activation was observed when watching a horror film and subliminal stimuli. The results of the study showed a different lateralization of the amygdala in men and women. Enhanced memory for the film was related to enhanced activity of the left, but not the right, amygdala in women, whereas it was related to enhanced activity of the right, but not the left, amygdala in men. Similarly, a study of decision-making ability in patients with unilateral amygdala damage suggested that men with right amygdala damage were more likely to be impaired in decision-making ability, while women with left amygdala damage were more likely to be impaired in decision-making ability. One study found evidence that, on average, women tend to retain stronger memories for emotional events than men.
Function
Connections
Variability in amygdala connectivity has been related to a variety of behaviors and outcomes such as fear recognition and social network size. A simple view of the information processing through the amygdala follows as: the amygdala sends projections to the hypothalamus, septal nuclei and BNST, the dorsomedial thalamus, the nuclei of the trigeminal nerve and the facial nerve, the ventral tegmental area, the locus coeruleus, and the laterodorsal tegmental nucleus.The basolateral amygdala projects to the nucleus accumbens, including the medial shell. Glutamatergic neurons in the basolateral amygdala send projections to the nucleus accumbens shell and core. Activation of these projections drive motivational salience. The ability of these projections to drive incentive salience is dependent upon dopamine receptor D1. The endocannabinoid system that produces lipoid neuromodulators has its specific receptors found in amygdalae.
File:Gray 718-amygdala.png|thumb|Coronal section of brain through intermediate mass of third ventricle. Amygdala is shown in purple.
The medial nucleus is involved in the sense of smell and pheromone-processing. It receives input from the olfactory bulb and olfactory cortex.The lateral amygdalae, which send impulses to the rest of the basolateral complexes and to the centromedial nuclei, receive input from the sensory systems. The centromedial nuclei are the main outputs for the basolateral complexes, and are involved in emotional arousal in rats and cats.
Emotional learning
In complex vertebrates, including humans, the amygdalae perform primary roles in the formation and storage of memories associated with emotional events. Research indicates that, during fear conditioning, sensory stimuli reach the basolateral complexes of the amygdalae, particularly the lateral nuclei, where they form associations with memories of the stimuli. The association between stimuli and the aversive events they predict may be mediated by long-term potentiation, a sustained enhancement of signaling between affected neurons. There have been studies that show that damage to the amygdala can interfere with memory that is strengthened by emotion. One study examined a patient with bilateral degeneration of the amygdala. He was told a violent story accompanied by matching pictures and was observed based on how much he could recall from the story. The patient had less recollection of the story than patients with functional amygdala, showing that the amygdala has a strong connection with emotional learning.Emotional memories are thought to be stored in synapses throughout the brain. Fear memories, for example, are considered to be stored in the neuronal connections from the lateral nuclei to the central nucleus of the amygdalae and the bed nuclei of the stria terminalis. These connections are not the sole site of fear memories given that the nuclei of the amygdala receive and send information to other brain regions that are important for memory such as the hippocampus. Some sensory neurons project their axon terminals to the central nucleus. The central nuclei are involved in the genesis of many fear responses such as defensive behavior, autonomic nervous system responses, neuroendocrine responses, etc. Damage to the amygdalae impairs both the acquisition and expression of Pavlovian fear conditioning, a form of classical conditioning of emotional responses. Accumulating evidence has suggested that multiple neuromodulators acting in the amygdala regulates the formation of emotional memories.
The amygdalae are also involved in appetitive conditioning. It seems that distinct neurons respond to positive and negative stimuli, but there is no clustering of these distinct neurons into clear anatomical nuclei. However, lesions of the central nucleus in the amygdala have been shown to reduce appetitive learning in rats. Lesions of the basolateral regions do not exhibit the same effect. Research like this indicates that different nuclei within the amygdala have different functions in appetitive conditioning. Nevertheless, researchers found an example of appetitive emotional learning showing an important role for the basolateral amygdala: The naïve female mice are innately attracted to non-volatile pheromones contained in male-soiled bedding, but not by the male-derived volatiles, become attractive if associated with non-volatile attractive pheromones, which act as unconditioned stimulus in a case of Pavlovian associative learning. In the vomeronasal, olfactory, and emotional systems, Fos proteins show that non-volatile pheromones stimulate the vomeronasal system, whereas air-borne volatiles activate only the olfactory system. Thus, the acquired preference for male-derived volatiles reveals an olfactory-vomeronasal associative learning. Moreover, the reward system is differentially activated by the primary pheromones and secondarily attractive odorants. Exploring the primary attractive pheromone activates the basolateral amygdala and the shell of nucleus accumbens but neither the ventral tegmental area nor the orbitofrontal cortex. In contrast, exploring the secondarily attractive male-derived odorants involves activation of a circuit that includes the basolateral amygdala, prefrontal cortex, and ventral tegmental area. Therefore, the basolateral amygdala stands out as the key center for vomeronasal-olfactory associative learning.