Network activity in hippocampal interneurons is regulated by GABA receptors

In the mammalian hippocampus, parvalbulim (a calcium binding albumin protein) expressing interneurons can be classified into a number of groups. Basket, axo-axonic, and oriens–lacunosum-moleculare (O-LM) are the main three groups, and they each innervate different regions of pyramidal cells in CA1. These are also each GABA-releasing interneurons, which is the main inhibitory neurotransmitter in the brain.

Klausberger et al (2002) analyzed the firing patterns of each of these cells in rat brains in vivo with respect to network activity, such as theta oscillations (4–8 Hz) involved in REM sleep, and sharp-wave-associated ripples (120–200 Hz) in slow wave sleep. Although the researchers adminstered urethane–ketamine anaesthesia on the rats, theta and high-frequency ripple waves stil occured, at mean frequencies of 123 +/- 11 Hz and 4.2 +/- 0.3 Hz, respectively.

They found a significant difference in the discharge frequency of these interneurons during theta oscillations and non-oscillation periods. In sharp wave oscillations, both pyramidal cells and basket cells fire at the moment of maximum amplitude of the episode, which produces an awe-inspiring cross-correlogram. The data strongly suggests that the different types of GABA interneurons have evolved to regulate the polarization of pyramidal cells depending on the brain’s current condition.

Glickfield et al (2008) recently tested hippocampal slices of 4-6 week old rats with patch pipets filled with 3 M NaCl in order to determine the effect of individual interneurons on their postsynaptic targets. The action potential of a single basket cell produced a local unitary field potential (uField) in the stratum pyramidale. When the postsynaptic region was treated with the GABA antagonist gabazine the the uField was stopped, indicating that potential was due to action in the synapse.

The positive uField in the stratum pyramidale necessitates a locally generated outward synaptic current, which means that the pyramidal cells must have experienced a hyperpolarization of their cell bodies. They additionally found that the hyperpolarizing effect of the GABA interneurons is not dependent on its location along the hippocampal axis. The GABA microcurcuits effect on pyramidal cells is an integral part of general network activity in the hippocampus at large, and a bottom-up approach is a useful tool for analyzing it.

Reference

Klausberger T, Magill PJ, Marton LF, Roberts JDB, Cobden PM, Buzsaki G, Somoavi P. 2002 Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 421:844-848.

Glickfeld LL, Roberts JD, Somogyi P, Scanziani M. 2008 Interneurons hyperpolarize pyramidal cells along their entire somatodendritic axis. Nature Neuroscience 12:21-23.