Although low in number
(~10% of the population), interneurons are highly diverse and can be subdivided
into several distinct types. The various types are active and produce
inhibition at different times and locations in the network and can regulate
when and where information can flow in neuronal circuits - in a similar manner
as traffic lights coordinate traffic on streets.
Our working hypothesis is, thus, that inhibitory interneurons coordinate neuronal activity and their diversity subserves a complex division of labor among the different types in networks of the brain.
A major mechanism of neuronal coordination is the generation of oscillatory activity. Oscillations ('brain waves') can be observed in the EEG and are thought to structure network activity. They provide rhythmically alternating temporal windows when neuronal discharge is high and low and thereby serve as timing signals.
We focus on the hippocampus, as this brain area is essential for learning and memory as well as spatial navigation; it is often affected in brain disorders (e.g. epilepsy, Alzheimer disease) and, last but not least, with its relatively simple laminated structure, it lends itself for experimental investigation.
Our experimental approach involves in vitro electrophysiological techniques, morphological and immunocytochemical analysis, and computational modeling.
The hippocampus: immunocytochemical staining for the calcium-binding proteins, calbindin (in green) and calretinin (in red) delineates main areas areas, the CA1, CA2, CA3 and the dentate gyrus (DG) as well as the layering in a horizontal section of the hippocampus . (from Hippocampal microcircuits 2010; Springer; Chapter 2)
Fast-spiking 'basket cells' are one of the most abundant interneuron types. It is considered as a rapid signaling element in the circuit which provides strong and precisely timed inhibition to soma and proximal dendrites of thousands of target cells. Note the characteristically dense local axonal arbor in cell body layer (g.c.l.) of the dentate gyrus. The inset shows the high-frequency discharge pattern of the neuron in response to a depolarizing current pulse. (Vida, unpublished.)
Fast and strong synapses promote
gamma-frequency oscillations in basket cell networks. Left: Camera
lucida reconstruction of a synaptically coupled basket cell pair in the dentate
gyrus. Middle: Action potentials in the presynaptic cell elicited fast
and large amplitude GABAA receptor-mediated IPSCs in the postsynaptic basket
cell. Right: The raster plot of action potentials in a simulated network
illustrates the rapid synchronization at gamma frequencies in an interneuron
network model incorporating when fast and strong mutual inhibitory synapses are
activated. (modified from Bartos et al., J.
Slow GABAB receptor-mediated inhibition in interneurons. A,B: Reconstructions of a perisomatic (a ‘basket cell’) and a dendritic inhibitory interneuron (a ‘bistratified cell’) in the hippocampal CA1 area. Insets show immunoreactivity for the calciumbinding protein parvalbumin (in green) of the somata of the biocytin filled cells (in blue pseudo color). Traces on the bottom show the pharmacologically-isolated slow inhibitory synaptic currents (IPSCs) elicited by extracellular stimulation in the voltage-clamped cells. (Booker and Vida, unpublished)