Table 1.

Anatomy and putative function of the gray matter hippocampal subfields.

Subfield	Clinical and preclinical notes
HATA	Part of the anterior HPC, bounded by the HPC folds, lateral ventricle, and alveus.11 Carries afferent and efferent signals between the rest of the HPC and the caudal amygdala and may send axonal collaterals to the PFC and hypothalamus.12 Plausible role in acquiring traumatic memories, behavioral and neuroendocrine response to threat, fear conditioning,13 and consolidation of contextual fear learning and memory.14 Projections to the HTH and PFC may relate to aggressive or defensive sexual behavior.12
ML	Sits above the SUB directly beneath the HPC fissure; traces the HPC folds along the CA fields and SUB.11 Interneuronal synaptic connections, serving probable role of transmission and integration of information across the HPC.15 Volume reduction has been observed in BP.16
DG	Tri-layered structure beginning near the middle of the HPC head.11 Supports neurogenesis, memory formation, and neuroplasticity; rapid acquisition in spatial memory involving pattern separation (young granule cells) or pattern completion (mature granule cells).17,18 Volumetric atrophy may be associated with chronic stress,19 BD,16 depression,20 PTSD,21,22 and schizophrenia.23,24
CA4	Hilus of the DG.11 Receives excitatory inputs from the cerebral cortex and interneurons of the DG; contains mRNA related to neurogenesis, complexins which are important for neurotransmission,25 and BDNF which is important for survival and maturation of neurons.26 Various reductions in mRNA concentrations are associated with BD, possibly dysregulating neuronal transmission.25
CA2/3	Superior to DG from posterior half of HPC head to the HT.11 Extensive interconnections among principal cells forming an autoassociative network, supports formation of arbitrary spatial association, temporary maintenance of spatial working memory, and spatial pattern completion.27–30 Supports mnemonic processes in the formation of accurate spatial memory.31 Implicated in spatial pattern separation via interaction of mossy fibers/DG29 and acquisition of context-dependent fear extinction but not context-dependent fear memories.32 Influences discrete gene expression.10 Volume alterations found in PTSD.21
CA1	Extends from SUB, ending near first HPC fold.11 Trisynaptic loop created by CA1 projections through SUB to entorhinal cortex relates to acquisition of memory and spatial learning.33 Context-dependent fear extinction and retrieval of contextual memory.24,32 Insult to CA1 impairs spatial navigation and working memory, but not reference memory.33,34 Reduction in volume seen with untreated schizophrenia.35
SUB	Three-layered allocortex, lateral to PrSUB and CA1.11 Part of limbic memory system, responsible for mnemonic processing,36 short-term memory retrieval, and spatial encoding.15 Stress response and inhibitory control over the HPA37 and implications in fear conditioning.38 Modulates epileptic discharges from the HPC.15 Atrophy implicated in early and advanced AD.39
PrSUB	BA27; periallocortex; heavily myelinated ML; sits along HPC fissure, anterior to retrosplenial region.11 Connection with excitatory synapses supports bursting behaviors.40 Short-term memory and processing of spatial location information.41 Implicated in and possible marker for AD.39
PaSUB	BA49; periallocortex; smaller than PrSUB and SUB; sits along HPC fissure.11 Continuous recognition memory for spatial navigation41,42 and integration of head direction.42 Inputs from GABAergic medial septal neurons and expression of cholinergic activity markers.43 Projecting neurons in thalamus, SUB, and PrSUB.44 Aids in determining spike timing relative to theta oscillations.45
HT	Not well studied, so difficult to make reliable annotations. Volume reductions reported with increasing duration/severity of BD.46 FMRI evidence shows that HT may activate with abnormal ease in PTSD.47

HPC: hippocampus; HATA: hippocampal–amygdala transition area; ML: molecular layer of the HPC; DG: granule cell and ML of the dentate gyrus; CA: cornu ammonis; SUB: subiculum; PrSUB: presubiculum; PaSUB: parasubiculum; HT: HPC tail; AD: Alzheimer’s disease; BA: Broadmann area; BDNF: brain derived neurotrophic factor; BP: bipolar disorder; HPA: hypothalamus–pituitary–adrenal axis; HTH: Hypothalamus; PFC: prefrontal cortex.