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Arousal
Certain areas in the brain, such as the hypothalamus, thalamus and basal ganglia, are involved in the regulation of arousal. The hypothalamus and other parts of the brain are also involved in regulating sleep, wakefulness, alertness, and memory consolidation. The hypothalamus and the basal ganglia tend to promote wakefulness by increasing the activation of the sleep-wake switch. The basal ganglia also inhibit sleep-related reflexes that would normally be activated by arousal. The thalamus is important for transmission of sleep-related signals from the hypothalamus, through the basal ganglia.
Long-term potentiation
Long-term potentiation (LTP) is a form of excitatory synapse modification that is thought to underlie learning and memory. It is induced and maintained by activity-dependent processes that are critical to activity-dependent synaptic plasticity that occurs during memory formation. LTP is hypothesized to underlie learning and memory as it is the cellular mechanism by which new synaptic connections are formed and existing connections strengthened. Mechanistically, LTP is hypothesized to be due to postsynaptic modification of glutamate receptors. Extracellular glutamate levels rise after learning during which neural activity increases which causes extrasynaptic glutamate release. This causes a non-synaptic rapid mechanism for glutamate receptor modification and increase. Synaptic modulation of glutamate receptors is hypothesized to be due to presynaptic activity-dependent changes that either decreases inhibition of glutamate release or increases glutamate release from presynaptic terminals. These presynaptic changes also lead to postsynaptic rapid changes in glutamate receptors.
Depression
A 2016 meta-analysis identified GABAergic signaling as a common cause of depression in animals.
Social interactions
Enlargement of the amygdala is associated with increased stress and reward responses to social interactions. This may result in a reduced sensitivity to the distress and pain of others, leading to a social deprivation model of depression. Greater amygdala volume is associated with an increased fear of social situations and poorer performance on tasks that measure social skills. The amygdala has reciprocal connections with the hypothalamus, which coordinates the sleep-wake cycle in the brain. Disruptions of the hypothalamus-amygdala-hypothalamus circuit may be a possible mechanism underlying social impairment in depression.
Genetic
Studies have shown that epigenetic mechanisms (the role of environmental factors) play a major role in the development of depression, with covalent modifications to DNA
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