Hippocampus

Anatomy

• In the medial temporal lobe, on the floor of the temporal horn of the lateral ventricle; head (pes), body and tail.
• Subfields: dentate gyrus, CA1–CA4, subiculum. The main input gateway is the entorhinal cortex (perforant path).
• Output: fimbria–fornix → mammillary bodies → anterior nucleus of the thalamus → cingulate (Papez circuit).
• Blood supply: PCA (hippocampal arteries) and the anterior choroidal artery.

Functions

• Encoding and consolidation of new declarative (episodic) memories.
• Spatial memory and navigation (place cells; entorhinal grid cells).
• Contextual memory: binding fear to context and letting context regulate the response.
• Pattern separation (dentate gyrus) and pattern completion (CA3).
• Negative feedback on the HPA axis (dense glucocorticoid receptors).

Connections and chemistry

• Entorhinal cortex (perforant path)
• Fornix → mammillary body → anterior thalamus (Papez circuit)
• Amygdala
• mPFC and PCC
• Hypothalamus (HPA feedback)
• Cholinergic septal inputs, glutamate

Development

Developmental course through childhood and adolescence.

• Infantile amnesia: early childhood memories do not last; hippocampal circuits (especially the dentate gyrus) mature in the preschool years.
• Volume increases through childhood and adolescence; anterior and posterior parts develop at different rates.
• Supportive parenting in early childhood has been linked to larger hippocampal volume (Luby et al., 2012).
• Chronic stress, poverty and abuse are associated with smaller hippocampal volume. Childhood maltreatment especially affects left CA2–CA3, CA4–dentate gyrus and the subiculum; the association is not explained by a history of depression or PTSD (Teicher et al., 2012; 193 young adults). These are the same sites where stress suppresses neurogenesis and prunes dendrites in animals. B

Clinical

• PTSD and chronic stress: smaller volume in adults; findings in children are less consistent.
• Depression: in ENIGMA (1,728 patients, 7,199 controls) the hippocampus is smaller (d = −0.14). The difference is marked in recurrent depression and absent at a first episode. It is larger when depression began at or before age 21 (d = −0.20) (Schmaal et al., 2016). Supports the importance of early onset and of preventing recurrence. A
• Temporal lobe epilepsy: mesial temporal sclerosis (may be linked to a history of prolonged febrile seizures).
• Early-onset schizophrenia, Down syndrome, prematurity: differences in hippocampal volume.

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• ECT: hippocampal volume increases by about 0.28% per session (281 patients), but this increase does not explain clinical response; volume change is not a response marker (Oltedal et al., 2018). A
• In depression, early and adequate treatment and prevention of recurrence fit the ENIGMA findings on recurrence and early onset (Schmaal et al., 2016). B
• For memory problems, cognitive rehabilitation and external memory aids (planner, reminders) are used after epilepsy surgery and in temporal lobe epilepsy.

Assessment

Neuropsychological tasks and measures that probe this region's function.

• Verbal list learning (RAVLT, CVLT-C)
• Story recall, Children’s Memory Scale (CMS)
• Rey figure delayed recall, virtual navigation

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Bilateral: anterograde amnesia (the case of H.M.); retrograde amnesia is temporally graded.
• Short-term memory and procedural memory are spared.
• Left lesions affect verbal memory more, right lesions visuospatial memory.

In the model

How this structure is defined in the 3D model, and the data source.

CerebrA hippocampus label.

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Teicher MH, Anderson CM, Polcari A. Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. PNAS 2012;109(9):E563–E572. Search PubMed
2. Schmaal L et al. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Mol Psychiatry 2016;21:806–812. Search PubMed
3. Oltedal L et al. Volume of the human hippocampus and clinical response following electroconvulsive therapy. Biol Psychiatry 2018. Search PubMed