MRC National Institute for Medical Research, London
Science for Health
Neuronal biophysical diversity is an emergent property of brain circuit organization
23 July 2012
Neurons show a range of biophysical properties that profoundly impact the computations they perform. For any given region, substructure or layer and cell type, neuronal morphology and connectivity varies. Even within cell type, there is diversity in morphology, expression of molecular markers and ion channels. Whether such diversity reflects biological noise inherent in the design of neuronal systems or perhaps a functional, dynamic process for regulating excitability at the cellular or even network level remains unclear.
The h-current (Ih), or sag potential, is one intrinsic biophysical property known to influence the input–output function of most principal nerve cell types. It has been shown that the variability in sag expression imposes diversity of function across the population of olfactory bulb mitral cells.
Troy Margrie (pictured) and colleagues have explored whether cell-to-cell variability in membrane potential sag might reflect differences between functional ensembles of neurons. They have taken advantage of the fact that the architecture of the olfactory bulb facilitates the identification of functionally discrete networks of mitral cells. Thus, in a brain slice preparation, individual principal mitral cells can be precisely linked to the functional circuit in which they operate in vivo.
The researchers have shown that the amplitude of hyperpolarization-evoked membrane potential sag recorded in mitral cells is not random but rather an emergent property of functionally discrete local circuits. Further analysis of a “monoclonal nose” mouse shows that the differences observed between mitral cell networks is dependent on the genetic diversity of olfactory sensory neuron input arriving from the periphery.
We suggest that cell-to-cell interactions among neurons belonging to the same sensory circuit influences their biophysical personalities, whereby cells processing the same kind of information are more similar than those neurons processing different information. In the olfactory bulb, the glomerular basis of this delineation may reflect a network-based gain control mechanism and result in correlated output patterning at the level of the network. The glomerulus-based diversity in expression of this intrinsic property in mitral cells appears a fundamental feature of the organisation and function of these olfactory circuits.
Troy Margrie
Diversity of sag potential amplitudes within and across mitral cell networks
Click image to view at full-size
a) Schematic of two possible organizing principles of mitral cell biophysical diversity. Each olfactory glomerulus receives genetically unique input, indicated in red, green and blue. The intrinsic, biophysical properties of mitral cells (represented by the different colored circles) within a glomerular network may be heterogeneous (left) or homogenous (right).
b) Histogram (fitted with a Gaussian) showing the distribution of sag potential amplitude (SPA) recorded across the mitral cell population (n = 105 cells). Traces are three examples recorded from cells belonging to the indicated bins. Scale bar is 600 ms and 15 mV.
c) Example morphologies of two simultaneously recorded mitral cells projecting to either different (c1) or the same glomerular networks (c2).
Original article
Kamilla Angelo, Ede A. Rancz, Diogo Pimentel, Christian Hundahl, Jens Hannibal, Alexander Fleischmann, Bruno Pichler, and Troy W. Margrie (2012)
A biophysical signature of network affiliation and sensory processing in mitral cells
Nature Epub ahead of print. Publisher abstract.
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