Download Inhibitory Control of Hippocampal Inhibitory Neurons

Hakkel Tamás
2017. 03. 30.
Inhibitory Control of
Hippocampal Inhibitory Neurons
Distribution of neurons specialized for inhibiting inhibitory neurons,
and their role played in the operation of hippocampus
The hippocampus is an ancient archicortical area that is reciprocally connected to almost all
sensory and associational areas through the entorhinal and perirhinal cortex. It was proven long ago
that hippocampus plays essential role in memory formation, but it was also well known that memories
are not directly stored in hippocampus e.g. because the human hippocampus is not much larger than
rat’s hippocampus, though human brain can store much more memories. Studies in the recent decades
revealed that hippocampus plays important role in processing and synchronizing inputs that is crucial
for long term potentiation and for the process of storing memories in neocortex.
Sensory input arriving to hippocampus is mainly processed by pyramidal cells of dentate gyrus,
CA3 and CA1 regions. These cells are organized into a recurrent network and also inhibitory cells helps
to refine output. However, these cells fire in a random manner, so they need synchronization because
long term potentiation requires accurate timing (action potentials must occur within 2-3 ms to
strengthen synapsis). In order to fulfil that requirement, hippocampus also contains perisomatic
inhibitory cells that are connected to the soma and initial segment of axons. When these inhibitors
fire, pyramidal cells are inhibited and these pyramidal cells are allowed to fire again when they do not
get inhibiting signals. A single perisomatic neuron (baskell cell or axo-axonic cell) innervates around a
thousand pyramidal cells.
On the other hand, these inhibitory cells are orchestrated by inhibition of GABAergic septohippocampal neurons. These cells are located in the septum and innervates the hippocampal cells with
long axons, so it is also called long-range interneurons. When these septal cells fire, they inhibit
perisomatic inhibitory cells, thus allow pyramidal cells to fire. Septal cells does not excite pyramidal
cells, although they helps pyramidal cells to depolarize their membrane by disinhibition. The septal
cells have a rhythmic activity by the pacemaker Na+ current. These individual pacemakers have to get
synchronized in phase to dictate a coherent rhythm to the hippocampus. That synchronization is done
by either by recurrent collateral interactions among septal units or hippocampal feedback.
The result of the rhythmic firing of septal cells is that the membrane potential of pyramidal cells
oscillates. That oscillation helps the long term potentiation and also filters noise. The oscillation is so
strong and widespread in brain that it can be measure even by EEG. On EEG recordings that oscillation
is called theta waves.