Hippocampus · Grey Matter

The hippocampus is a curved strip of cortex on the inner face of each temporal lobe that turns experiences into lasting memories: it binds the sights, sounds, places and feelings of an episode together so that the episode can be recalled later, and it builds the map that lets an animal know where it is.

Hippocampus. The hippocampus is a curved strip of cortex on the inner face of each temporal lobe that turns experiences into lasting memories: it binds the sights, sounds, places and feelings of an episode together so that the episode can be recalled later, and it builds the map that lets an animal know where it is.

Its name comes from the Venetian anatomist Aranzi, who in 1587 compared its shape to a seahorse (Greek hippokampos, from hippos, horse, and kampos, sea monster). It receives the output of the whole association cortex through the entorhinal cortex and sends it back, which makes it a convergence point. The leading account treats it as an index rather than an archive: the content of a memory stays in the cortical areas that processed it, and the hippocampus stores the pattern that ties those scattered pieces together, so that a cue can reactivate the whole.

Without it no new episode is kept. Bilateral removal in the patient H.M. left him unable to form new lasting memories of events and facts while his older knowledge, his language and his skills remained.

Over time a memory depends less on it. Through memory consolidation, replayed during sleep, the cortical pieces become linked directly; how far this goes for vivid personal episodes is still debated.

It is among the first structures to shrink in Alzheimer's disease, and its scarring (hippocampal sclerosis) is the most common lesion behind temporal lobe epilepsy.

Its neurons include place cells, which fire when an animal is at a particular spot, the basis of the map used to find a parked car or lost keys.

Questions: How does cortisol switch off its own release, and what is the hippocampus doing in that loop? Cortisol binds glucocorticoid receptors in the pituitary and the hypothalamus, where it suppresses ACTH and CRH, a classic negative feedback. The hippocampus, rich in the same receptors, adds a higher level of brake: it inhibits the paraventricular nucleus through relays, and the medial prefrontal cortex does the same, while the amygdala pushes the axis up. When the brake weakens, cortisol stays high for longer after each stress, which is one reason chronic stress and hippocampal damage are studied together. Why are emotional events remembered better than ordinary ones? An arousing event releases adrenaline and cortisol and activates noradrenaline in the basolateral amygdala, which then strengthens the consolidation of the memory in the hippocampus and the cortex. McGaugh and colleagues showed that blocking noradrenaline receptors in the amygdala removes the advantage of emotional memories, and that stimulating them after learning enhances ordinary ones. People with damage to both amygdalae remember emotional and neutral stories about equally well. The enhancement helps the gist of the event more than every detail, and vivid memories can still be wrong. Which areas work together when you search for the keys you put down somewhere? The hippocampus tries to recover the episode of putting them down, with its place and time, using the map built by its place cells and the grid cells of the entorhinal cortex. The posterior parietal cortex turns the remembered location into a position relative to your body and guides the eyes and steps toward it. The dorsolateral prefrontal cortex organises the search (where was I last, which rooms are already checked) and keeps the goal in mind while attention moves from place to place. Why is the hippocampus so often where focal seizures start? The hippocampus is built to change: densely recurrent excitatory circuits that strengthen quickly with use, which makes it good at storing associations and also prone to runaway synchronous firing. It is vulnerable to the injuries that start epilepsy (prolonged febrile seizures, hypoxia, encephalitis), and the most common lesion found in surgery for drug-resistant temporal lobe epilepsy is hippocampal sclerosis: loss of neurons, scarring and rewiring such as the sprouting of mossy fibres back onto their own cells. Seizures starting there often begin with a rising feeling in the stomach, déjà vu or fear, the signature of the medial temporal lobe. How does the hippocampus hand a memory over to the cortex? During an experience each feature is processed where it belongs (the face in visual cortex, the voice in auditory cortex, the feeling through the amygdala), and the hippocampus stores a compact index of which cortical patterns were active together. When a cue later reactivates the index, it reactivates the whole cortical pattern, and that is recall. Every reactivation, in waking rest and above all in sleep, also strengthens the direct links between the cortical pieces themselves. After weeks to years many memories can be retrieved from the cortex alone, the way a book can be found on its shelf once the librarian's card is no longer needed. Was the Papez circuit the circuit of emotion, as first proposed? In 1937 James Papez proposed a loop from the hippocampus through the fornix to the mammillary bodies of the hypothalamus, on to the anterior thalamus, to the cingulate cortex and back to the hippocampus, as the anatomical basis of emotion. Later work showed that the loop matters above all for memory: damage at several of its stations (the hippocampus, the mammillary bodies in Korsakoff syndrome, the anterior thalamus) causes amnesia rather than a loss of emotion. The amygdala, which Papez left out, turned out to be the structure most closely tied to emotional learning. Are some brain regions plastic and others fixed? Every region changes with experience; they differ in what changes and how fast. The hippocampus and the neocortex are built to rewire quickly and constantly, storing new episodes and remapping after injury, while the amygdala also learns fast (fear conditioning is long-term potentiation in its lateral nucleus) but holds what it learns stubbornly. Brainstem and spinal reflexes are the most stable, yet still adjustable: the reflex that steadies the eyes during head movement recalibrates within days to new glasses, through the cerebellum and the brainstem's vestibular nuclei. A ranking of whole regions as plastic or rigid is therefore a simplification, useful only as a rough contrast between circuits designed to learn and circuits designed to be reliable. What does the medial septum do for the hippocampus? The medial septum sends cholinergic and GABAergic fibres through the fornix to the hippocampus and acts as the pacemaker of its theta rhythm, a 4 to 10 Hz oscillation present when an animal explores or attends. Theta organises the timing of hippocampal firing, including the sequences of place cells, and lesions or inactivation of the medial septum abolish it and impair spatial memory. The septum thus gives the memory system a clock, while the lateral septum carries the hippocampus's output toward the hypothalamus. Why does Alzheimer's disease often first show as asking the same question again? The disease attacks the entorhinal cortex and the hippocampus early, the gateway through which new experiences become episodic memories. A person can still hold the answer in working memory for a few seconds and understand it perfectly, but it is not stored, so a few minutes later the question feels new and is asked again. Older memories and well-practised knowledge, already held by the cortex, last longer, which is why the early picture resembles a mild anterograde amnesia. Why did the patient H.M. keep his old memories but form no new ones? The 1953 operation removed most of both hippocampi with the surrounding medial temporal cortex, the structures that bind a new experience into a lasting trace, so nothing new could be stored once his attention moved on. Knowledge consolidated years earlier had already been reorganised into the cortex, which was untouched, so his vocabulary, general knowledge and childhood memories remained. The sparing was partial: he lost much of the decade before the operation, and later testing found that even his older personal memories had lost their vivid detail while keeping their facts. That gradient is the evidence that the hippocampus is needed for storing and for a time afterwards, but not forever for every kind of memory. Why is the hippocampus the most common starting point of focal epilepsy that resists drugs? The hippocampus is built for strong recurrent excitation and plasticity, which serve memory and also let activity spread and synchronise easily. Its pyramidal cells, CA1 above all, are among the most vulnerable in the brain to injury such as a prolonged febrile seizure, and their loss leaves a shrunken, scarred hippocampus, called hippocampal sclerosis. In the surviving circuit, the mossy fibres of dentate granule cells sprout back onto granule cells and form recurrent excitatory loops, and some inhibitory interneurons are lost, so the tissue becomes easier to synchronise and harder to calm with drugs.