hippocampus

**Anatomy** - Located in the medial temporal lobe, forming the floor of the temporal horn of the lateral ventricle. It is part of the hippocampal formation: dentate gyrus, hippocampus proper (CA1–CA4, also called cornu ammonis), and subiculum. The entorhinal cortex (parahippocampal gyrus) is the main gateway of input and output. - It is archicortex with 3 layers, unlike the 6-layered neocortex. - Main circuit (trisynaptic loop): entorhinal cortex → (perforant path) → dentate gyrus → (mossy fibers) → CA3 → (Schaffer collaterals) → CA1 → subiculum → entorhinal cortex/neocortex. - Output travels via the fornix → mammillary bodies → anterior nucleus of the thalamus → cingulate gyrus → entorhinal cortex. This is the **Papez circuit**.

**Function** - Consolidation of short-term memory into long-term declarative memory (episodic and semantic). Long-term memories are stored in the neocortex, not in the hippocampus. - Spatial memory and navigation (place cells). - Procedural memory (motor skills, e.g., riding a bike) is **not** hippocampal. It involves the basal ganglia and cerebellum. - Long-term potentiation (LTP) is the cellular basis of learning and memory. It is NMDA receptor–dependent (glutamate) and occurs prominently at CA1 synapses. - Adult neurogenesis occurs in the subgranular zone of the dentate gyrus. - It modulates the HPA axis through negative feedback. Chronic stress or high cortisol causes hippocampal atrophy (seen in PTSD and depression).

**Clinical significance** - **Alzheimer disease**: early atrophy of the hippocampus and entorhinal cortex gives early short-term memory loss. Findings include neurofibrillary tangles (hyperphosphorylated tau), β-amyloid plaques, and reduced ACh from loss of the nucleus basalis of Meynert. Treat with acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine (NMDA antagonist). - **Hypoxia/ischemia**: CA1 pyramidal neurons (Sommer sector) are the most vulnerable, followed by Purkinje cells of the cerebellum. Global ischemia causes selective neuronal necrosis (red neurons at 12–24 h). - **Bilateral hippocampal lesions** (e.g., HSV-1 encephalitis, herpes affects the temporal lobes; bilateral medial temporal resection as in patient H.M.): **anterograde amnesia** with relatively preserved remote memory, procedural memory, and intelligence. - **Wernicke-Korsakoff**: thiamine deficiency damages the mammillary bodies and the medial dorsal thalamus (Papez circuit), producing anterograde and retrograde amnesia with confabulation. - **Mesial temporal sclerosis** (hippocampal sclerosis): the most common cause of temporal lobe epilepsy (focal impaired-awareness seizures with aura, automatisms, déjà vu). It is often associated with prior febrile seizures. Treat refractory cases with temporal lobectomy. - **Transient global amnesia**: sudden anterograde amnesia lasting <24 h in older adults. Workup is normal, and it is thought to involve transient hippocampal dysfunction. - **Limbic encephalitis** (anti-Hu, anti-NMDA receptor, anti-LGI1): subacute memory loss, seizures, and psychiatric symptoms. It can be paraneoplastic (e.g., small cell lung cancer, ovarian teratoma for anti-NMDAR). - **Pathologic findings**: Negri bodies (rabies) are classically found in hippocampal pyramidal cells and Purkinje cells. Hirano bodies (eosinophilic rod-like inclusions) are seen in Alzheimer disease. Cowdry A inclusions are seen in HSV encephalitis.

**High-yield pearls** - Hippocampus = declarative memory consolidation (new memories); amygdala = emotional memory/fear; basal ganglia/cerebellum = procedural memory. - Anterograde amnesia = can't form new memories; retrograde amnesia = loss of previously formed memories. - The fornix is the major efferent tract; the mammillary bodies are part of the Papez circuit. - Think CA1 for ischemia, CA3 for seizure-related excitotoxic damage, and the dentate gyrus for neurogenesis.