Hippocampus and the limbic system.
The chart at left shows the comparative organization and complexity (if not size) of the brain as developed through different species. One of the things to which I'd like to call attention is the cerebrum and that little bulb sticking out (and left) from the bottom of the brain. That's the olfactory bulb, and it is connected to the most primitive part of the brain – pyriform cortex, which ultimately ends up on the inner surface of the human Temporal Lobe. The cerebrum of fish, reptile and bird contain a structure which is functionally analogous to the mammalian hippocampus, entorhinal cortex, and other elements which come to form the "limbic system." In fact, if one presupposes a connection between olfaction/nose/rhinal, it may suggest the origins of the rhinal, perirhinal and entorhinal cortices. It would be *wrong* but a fanciful association nonetheless. [The "rhinal" areas are around the "Rhinal Sulcus" which is a groove on the surface of the Temporal Lobe which an early anatomist thought looked like a nose!]
The most primitive brain had a single layer of neurons on the outer surface, compared to the 6-layer neocortex of mammals, and was termed "archicortex" or primitive cortex. Development of the "new" neocortex over the archicortex resulted in the primitive areas folding under and into the ventral (bottom) brain regions. This is one reason why hippocampus – the most notable of the archicortex structures – is very large and near the top of brain in rodents (and thus, *very* easy to study) but rather small and convoluted into the inner Temporal Lobe in humans.
The limbic system (below right) connects olfactory senses to the rest of the brain, is intricately involved in memory processing, provides a "timing" signal or oscillation that is critical to coordinating memory storage, recall, movement and sense of time, and processes some aspects of emotion.
The second thing I recall learning is the importance of the sense of smell to memory. Olfactory inputs are the single most numerous (and only *direct*) sensory input to hippocampus. The sense of smell is a strong trigger of association in memory (and we will get to that in a couple of days) – and is thought to be responsible for the sense of Déjà vu – in which a smell triggers memory, even in a novel situation, providing a sense of *almost* recalled memory and familiarity. We now know that smell, fear, stress, emotion are all intricately linked, and that linkage is processed through the limbic system and provides emotional context for memory.
Which brings us to the hippocampus. While not the root of all memory (there is extremely short-term memory processing in Frontal Lobe, as well as in the basal ganglia) it is the site of most of the memory processing for working memory (i.e. long enough to complete a task) and conversion to long-term memory. One of the important features of hippocampal neurons is theta rhythm. Theta is a 6-to-12 cycles-per-second oscillation of groups of neurons in the medial septum (hypothalamus) that acts as a "clock" for a lot of activities in hippocampus. Recording electrodes placed in rat hippocampus reveal a strong wave of activity every 80 to 200 milliseconds as a volley of neurons fire action potentials down the long axons terminating in hippocampus. Hippocampal neurons fire in various relationships and the actual "phase" of firing can be used to represent specific information.
For many years it was known that human hippocampus processed *new* memory. The famous case of patient H.M., who had the medial temporal lobe (including hippocampus) removed from both hemispheres to halt his epilepsy, showed that without a hippocampus, a patient was unable to make and hold memory for more than 10-15 minutes. However, in rodents, the primary type of memory processed by hippocampal was thought to be spatial (i.e. running a maze). Since theta rhythm increased in power (and slightly in frequency) with movement, and the observation that hippocampal neurons fired only in certain places within the environment (and phases of the Theta oscillation), hippocampus *must* be the site of a cognitive *map* of the environment! We have since discovered that such a map is merely one form of *association* between the animals environment and its behavior, and hence an important, but not exclusive, function of hippocampus. Indeed, the Theta Rhythm appears to be crucial in setting the sequence of associations, and hence the sense of time and order of memories.
The hippocampus receives inputs from all of the sensory association areas of the brain, as well as prefrontal cortex and striatum. Outputs from hippocampus lead back to the same areas, plus motor planning and interpretation. There are some who *still* wonder if hippocampus isn't the missing "Director" of all brain function, although as mentioned in last Monday's blog, that role is best filled by the Frontal Lobe. Still, the hippocampus is placed to receive and *associate* most, if not all, of the sensory information in the brain, and use it in the encoding of memory. Without hippocampus, there is no short term (longer than a minute) and no long term memory. If the hippocampus is damaged or inactivated (using anesthetics) between behavior and the next sleep period, the working memory is not converted to permanent long-term storage. While memory recall is still possible without the hippocampus, they ability to use associations to assist in recall is impaired.
From here, the next logical step is to talk further about memory and amnesia, and we will do that in the next series of blogs on amnesia, memory, and abnormal memory processes.
So *remember* to tune in next time!