Genetic determinants of barrel cortex map formation (Commentary on She et al.)
Article first published online: 30 MAR 2009
© The Authors (2009). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 29, Issue 7, page 1378, April 2009
How to Cite
Petersen, C. (2009), Genetic determinants of barrel cortex map formation (Commentary on She et al.). European Journal of Neuroscience, 29: 1378. doi: 10.1111/j.1460-9568.2009.06744.x
- Issue published online: 30 MAR 2009
- Article first published online: 30 MAR 2009
Primary visual (V1), auditory (A1) and somatosensory (S1) cortices contain well-ordered maps of the sensory periphery. The retinotopic (V1), tonotopic (A1) and somatotopic (S1) maps are largely determined through the arrangement of incoming thalamocortical projections. Whereas it is clear that activity-independent (Molnar et al., 2002) genetically-programmed mechanisms involving molecular gradients (Fukuchi-Shimogori & Grove, 2001) play a major role in the establishment of these thalamocortical maps during development, there is also strong evidence indicating that activity contributes substantially to cortical map refinement. A convenient model system for investigating cortical map formation and plasticity is the mouse primary somatosensory barrel cortex (recently reviewed by Petersen, 2007). In this cortical region, each mystacial vibrissa on the snout of the rodent is represented by an anatomically defined structure in layer 4, termed a ‘barrel’, and the resulting somatotopic barrel map can be visualised through a large number of simple stains.
In this issue, She et al. (2009) find that the barrel map is partially disrupted in metabotropic glutamate receptor type 5 (mGluR5) knockout mice, in good agreement with a previous study (Hannan et al., 2001). Of particular interest are alterations in the representation of the large posterior vibrissae that are actively swept backwards and forwards during whisking behaviour in exploring mice. For these whiskers, the thalamocortical afferents in mGluR5 knockout mice segregate normally into clusters in layer 4, a process which is thought to be a key event driving barrel formation. However, the organisation of postsynaptic neurons in layer 4 is disturbed in knockout mice. In wild type and heterozygous mice, the somata of layer 4 neurons form cell-dense walls surrounding each of the thalamocortical axon clusters, but this pattern is completely absent in mGluR5 knockout mice. This clearly indicates that there are at least two separable steps for barrel formation, one being the segregation of the presynaptic thalamocortical axons (which appears to be normal in mGluR5 knockout mice) and a second step to position the layer 4 cell bodies into a barrel map (which is disrupted in mGluR5 knockout mice).
In wild type and heterozygous mice, the neurons located in barrel walls exhibit highly asymmetric dendrites pointing towards the barrel center, which presumably contribute to the sharpening of receptive fields. Such oriented dendrites were found much less frequently in mGluR5 knockouts. Perhaps resulting from these unpolarised neurons sending their dendrites into more than one thalamocortical cluster, She et al. (2009) find unusual short latency responses to deflection of more than one whisker in the knockout mice.
She et al. (2009) also studied thalamocortical synaptic transmission and plasticity in vitro revealing several differences in mGluR5 knockout mice. Although presynaptic thalamocortical function and AMPA-receptor-dependent signalling appeared normal, postsynaptic differences were found in the kinetics of NMDA-receptor-dependent currents, which were faster in the mGluR5 knockout mice. Perhaps more importantly, LTP was absent in these knockout mice, whereas LTD was enhanced.
It is intriguing to speculate that these changes in synaptic plasticity in mGluR5 knockout mice might contribute to the disorganised dendritic structure of the layer 4 neurons. Perhaps LTP- and LTD-like phenomena during development help stabilise dendrites connected to the ‘correct’ principal whisker thalamocortical cluster and might help destabilise dendrites pointing into the ‘wrong’ neighbouring thalamocortical clusters.
The effects of mGluR5 knockout on the barrel map are strikingly similar to those in PLC-β1 knockout mice (Hannan et al., 2001) and cortex-specific NMDAR1 knockout mice (Iwasato et al., 2000) suggesting potential convergence in their postsynaptic signalling pathways, at least in their roles for barrel formation. The new results from She et al. (2009) further our understanding of how layer 4 barrels form, and raise questions that will doubtless continue to fascinate researchers for many years to come.
- 2001) Neocortex patterning by the secreted signaling molecule FGF8. Science, 294, 1071–1074. & (
- 2001) PLC-beta1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex. Nat. Neurosci., 4, 282–288. , , , , , , , , & (
- 2000) Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature, 406, 726–731. , , , , , , , & (
- 2002) Normal development of embryonic thalamocortical connectivity in the absence of evoked synaptic activity. J. Neurosci., 22, 10313–10323. , , , , & (
- 2007) The functional organization of the barrel cortex. Neuron, 56, 339–355. (
- 2009) Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway. Eur. J. Neurosci., 29, 1379–1396. , , , , , , & (