Amygdala: Function and neural basis

This review summarizes our current understanding of the amygdala. As an important part of the limbic system, the amygdala is highly sensitive to environmental stimuli such as sounds. Although the responses of amygdala neurons to sounds are usually not as robust as those of neurons in the primary auditory cortex, the lowest response thresholds of these neurons are consistent with the behavioral audiogram. When a threat is detected through sensory information processing, it immediately triggers a fight-or-flight response, such as freezing and heart rate increase. By learning and remembering environmental events (especially those that may cause harm) and its effects on various instinctive behaviors (such as sexual impulse and maternal behaviors) as well as emotional expressions (such as fear and aggression), it plays a crucial role in the survival and continuation of the species. The response of amygdala neurons to environmental sounds is often composed of an early sharp response component and a late slow response component. The early response is responsible for rapid processing of meaningful information (such as the presence of danger), while the late response can be related to emotional processing. Indeed, the early response of the amygdala is enhanced when there are predator cues or during fear conditioning. Sounds with different emotional tones can trigger different response patterns in the amygdala. It is well documented that the amygdala plays a crucial role in Pavlovian fear conditioning. During this process, both the conditioned stimulus (CS) and the unconditioned stimulus (US) converge on the neurons in the lateral amygdala (LA), thereby activating the central amygdala (CeA) and triggering the conditioned response. Interestingly, the amygdala can be associated with various psychiatric disorders, such as anxiety disorders, depression, and even tinnitus. The amygdala is composed of the LA, the basal lateral amygdala (BLA), the basal medial amygdala (BMA), the CeA, the medial amygdala (MeA) and the cortical amygdala (CoA). The lateral amygdala complex (LA, BLA and BMA) is mainly composed of glutamatergic pyramidal neurons (PNs, accounting for 70%-85% of the total neurons), while the CeA mainly contains GABAergic neurons (>90% of the neurons). Glutamate and GABA are the two main neurotransmitters in the amygdala. In addition, the neural activity of the amygdala can also be regulated by various neurotransmitters, neuromodulators and hormones from other areas of the brain, such as acetylcholine (ACh), dopamine (DA), serotonin (5-HT), norepinephrine (NE), and glucocorticoids. The LA receives sensory information from both the thalamus (the fast low road) and the cortex (the slow high road). The PNs in the LA can directly stimulate the projection neurons in the CeA, thereby triggering corresponding behavioral responses, such as urgent response or fear conditioning. The LA PNs can also project to the BLA and BMA for further information processing. The PNs in the BLA/BMA can directly project to the CeA or project to the hippocampus and the prefrontal cortex for processing. The rapid fear conditioning can be achieved through the fast low road. However, the information processing results through the slow high road may modulate or override the initial fear response through the fast low road. More than 90% of the neurons in the CeA are inhibitory neurons, inhibiting neural activity of the brainstem. For example, in the context of freezing behavior, they can inhibit the neural activity of the pre-Bötzinger complex, thereby suppressing breathing. The CeA also contains excitatory neurons (<10%). They can excite neurons in the hypothalamus or in the caudal pontine reticular nucleus, triggering the fight-or-flight response or leading to an enhanced auditory startle response.