Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway

Abstract

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the development of cortical sensory maps. However its precise roles in the synaptic function and plasticity of thalamocortical connections remain unknown. Here we first show that in mGluR5 knockout mice bred onto a C57BL6 background cyto-architectonic differentiation into barrels is missing, but the representations for large whiskers are identifiable as clusters of thalamocortical afferents. The altered dendritic morphology of cortical layer IV spiny stellate neurons in mGluR5 knockout mice implicates a role for mGluR5 in the dendritic morphogenesis of excitatory neurons. Next, in vivo single unit recordings of whisker evoked activity in mGluR5 knockout adults demonstrated a preserved topographical organization of the whisker representation, but a significantly diminished temporal discrimination of center to surround whiskers in the responses of individual neurons. To evaluate synaptic function at thalamocortical synapses in mGluR5 knockout mice, whole-cell voltage clamp recording was conducted in acute thalamocortical brain slices prepared from postnatal day 4-11 mice. At mGluR5 knockout thalamocortical synapses, NMDA currents decayed faster and synaptic strength was more easily reduced, but more difficult to strengthen by Hebbian-type pairing protocols, despite a normal developmental increase in AMPAR-mediated currents and presynaptic function. We have therefore demonstrated that mGluR5 is required for synaptic function/plasticity at thalamocortical synapses as barrels are forming and we propose that these functional alterations at the thalamocortical synapse are the basis of the abnormal anatomical and functional development of the somatosensory cortex in the mGluR5 knockout mouse.

Genetic determinants of barrel cortex map formation (Commentary on She et al.)

“…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.…”

“…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.…”

“…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.…”

“…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.…”

“…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.…”