Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory.

The amygdalar nuclear complex and hippocampal/parahippocampal region are key components of the limbic system that play a critical role in emotional learning and memory. This Review discusses what is currently known about the neuroanatomy and neurotransmitters involved in amygdalo-hippocampal interconnections, their functional roles in learning and memory, and their involvement in mnemonic dysfunctions associated with neuropsychiatric and neurological diseases. Tract tracing studies have shown that the interconnections between discrete amygdalar nuclei and distinct layers of individual hippocampal/parahippocampal regions are robust and complex. Although it is well established that glutamatergic pyramidal cells in the amygdala and hippocampal region are the major players mediating interconnections between these regions, recent studies suggest that long-range GABAergic projection neurons are also involved. Whereas neuroanatomical studies indicate that the amygdala only has direct interconnections with the ventral hippocampal region, electrophysiological studies and behavioral studies investigating fear conditioning and extinction, as well as amygdalar modulation of hippocampal-dependent mnemonic functions, suggest that the amygdala interacts with dorsal hippocampal regions via relays in the parahippocampal cortices. Possible pathways for these indirect interconnections, based on evidence from previous tract tracing studies, are discussed in this Review. Finally, memory disorders associated with dysfunction or damage to the amygdala, hippocampal region, and/or their interconnections are discussed in relation to Alzheimer's disease, posttraumatic stress disorder (PTSD), and temporal lobe epilepsy.