Neural mechanisms of extinction learning and retrieval have been extensively studied, revealing that extinction, like other forms of learning, occurs in three phases: acquisition, consolidation, and retrieval. Each phase involves specific brain structures and molecular mechanisms. The amygdala, prefrontal cortex, and hippocampus play key roles in these processes. Extinction is a form of inhibition, not erasure of the original memory, and involves complex interactions between these brain regions. Extinction acquisition involves the initial learning that occurs when conditioned responses decrease during extinction training. This process is influenced by NMDA receptors, calcium currents, and other molecular pathways. The basolateral amygdala (BLA) is involved in the acquisition of extinction, as local infusions of NMDA antagonists and kinase inhibitors prevent extinction. However, the exact site of extinction acquisition remains unclear, as it may be distributed across multiple structures. Consolidation of extinction involves stabilizing the long-term memory for extinction. This process is supported by molecular cascades and requires protein synthesis in the BLA. The prefrontal cortex, particularly the infralimbic (IL) region, is also involved in consolidation, as its activation is necessary for effective extinction retrieval. The hippocampus plays a role in contextual modulation of extinction, and its activity is necessary for the renewal of fear in non-extinction contexts. Retrieval of extinction involves the expression of an inhibitory memory and is highly context-dependent. The IL region of the prefrontal cortex integrates contextual information from the hippocampus to determine extinction retrieval. Inhibitory networks within the amygdala, including intercalated cells, are involved in the expression of extinction. The hippocampus is also crucial for contextual modulation of extinction, and its activity is necessary for the consolidation of extinction memory. Extinction of appetitive responses involves similar neural mechanisms as fear extinction, with the BLA and prefrontal cortex playing key roles. The vmPFC is involved in the retrieval of appetitive extinction, and its modulation can influence the return of drug-seeking behavior following extinction. Clinical implications of extinction research are significant, as anxiety disorders and addictions are often treated with extinction-based exposure therapies. Pharmacological agents such as D-cycloserine (DCS) have been shown to enhance extinction in animals and may be useful as adjuncts to exposure therapy in humans. Other drugs, including inhibitors of endocannabinoid breakdown and glucocorticoids, are also being investigated for their potential to enhance extinction. Extinction and reconsolidation are related processes, with reconsolidation involving the reactivation of a memory to maintain it. Both processes share similar molecular mechanisms, including protein synthesis, NMDA receptors, and MAPk. Understanding these processes is crucial for developing effective treatments for anxiety disorders and addictions.Neural mechanisms of extinction learning and retrieval have been extensively studied, revealing that extinction, like other forms of learning, occurs in three phases: acquisition, consolidation, and retrieval. Each phase involves specific brain structures and molecular mechanisms. The amygdala, prefrontal cortex, and hippocampus play key roles in these processes. Extinction is a form of inhibition, not erasure of the original memory, and involves complex interactions between these brain regions. Extinction acquisition involves the initial learning that occurs when conditioned responses decrease during extinction training. This process is influenced by NMDA receptors, calcium currents, and other molecular pathways. The basolateral amygdala (BLA) is involved in the acquisition of extinction, as local infusions of NMDA antagonists and kinase inhibitors prevent extinction. However, the exact site of extinction acquisition remains unclear, as it may be distributed across multiple structures. Consolidation of extinction involves stabilizing the long-term memory for extinction. This process is supported by molecular cascades and requires protein synthesis in the BLA. The prefrontal cortex, particularly the infralimbic (IL) region, is also involved in consolidation, as its activation is necessary for effective extinction retrieval. The hippocampus plays a role in contextual modulation of extinction, and its activity is necessary for the renewal of fear in non-extinction contexts. Retrieval of extinction involves the expression of an inhibitory memory and is highly context-dependent. The IL region of the prefrontal cortex integrates contextual information from the hippocampus to determine extinction retrieval. Inhibitory networks within the amygdala, including intercalated cells, are involved in the expression of extinction. The hippocampus is also crucial for contextual modulation of extinction, and its activity is necessary for the consolidation of extinction memory. Extinction of appetitive responses involves similar neural mechanisms as fear extinction, with the BLA and prefrontal cortex playing key roles. The vmPFC is involved in the retrieval of appetitive extinction, and its modulation can influence the return of drug-seeking behavior following extinction. Clinical implications of extinction research are significant, as anxiety disorders and addictions are often treated with extinction-based exposure therapies. Pharmacological agents such as D-cycloserine (DCS) have been shown to enhance extinction in animals and may be useful as adjuncts to exposure therapy in humans. Other drugs, including inhibitors of endocannabinoid breakdown and glucocorticoids, are also being investigated for their potential to enhance extinction. Extinction and reconsolidation are related processes, with reconsolidation involving the reactivation of a memory to maintain it. Both processes share similar molecular mechanisms, including protein synthesis, NMDA receptors, and MAPk. Understanding these processes is crucial for developing effective treatments for anxiety disorders and addictions.