Exuberant thalamocortical axon arborization in cortex-specific NMDAR1 knockout mice

Abstract

Development of whisker-specific neural patterns in the rodent somatosensory system requires NMDA receptor (NMDAR)-mediated activity. In cortex-specific NR1 knockout (CxNR1KO) mice, while thalamocortical afferents (TCAs) develop rudimentary whisker-specific patterns in the primary somatosensory (barrel) cortex, layer IV cells do not develop barrels or orient their dendrites towards TCAs. To determine the role of postsynaptic NMDARs in presynaptic afferent development and patterning in the barrel cortex, we examined the single TCA arbors in CxNR1KO mice between postnatal days (P) 1-7. Sparsely branched TCAs invade the cortical plate on P1 in CxNR1KO mice as in control mice. In control animals, TCAs progressively elaborate patchy terminals, mostly restricted to layer IV. In CxNR1KO mice, TCAs develop far more extensive arbors between P3-7. Their lateral extent is twice that of controls from P3 onwards. By P7, CxNR1KO TCAs have significantly fewer branch points and terminal endings in layers IV and VI but more in layers II/III and V than control mouse TCAs. Within expansive terminal arbors, CxNR1KO TCAs develop focal terminal densities in layer IV, corresponding to the rudimentary whisker-specific patches. Given that thalamic NMDARs are spared in CxNR1KO mice, the present results show that postsynaptic NMDARs play an important role in refinement of presynaptic afferent arbors and whisker-specific patterning in the developing barrel cortex. Indexing termsbarrels; barreloids; trigeminal system; somatosensory cortex; region-specific gene knockout A conspicuous feature of the rodent primary somatosensory cortex is the presence of neural patterns within face and digit representation regions of the body map. Patches of thalamocortical afferent (TCA) arbors and their postsynaptic partners form discrete modules that replicate the patterned distribution of whiskers on the contralateral snout. These cellular modules are termed "barrels" (Woolsey and Van der Loos, 1970). Whisker and digit-related patterns are first established in the brainstem somatosensory nuclei, then in the ventrobasal nuclear complex (VB) of the dorsal thalamus, and finally in the layer IV of the neocortex. Such cellular modules are called "barreloids" in the VB, and "barrelettes" in the brainstem (Woolsey and Van der Loos, 1970;Van der Loos, 1976;Ma and Woolsey, 1984 Van der Loos, 1986;Woolsey, 1990;O'Leary et al., 1994;Killackey et al., 1995). Several lines of evidence also indicate that somatosensory periphery-related neural maps and patterns are conveyed to target cells by the afferents at each synaptic relay station Jhaveri, 1990, 1992a, b;Senft and Woolsey, 1991).In recent years, a number of transgenic and knockout (KO) mouse models have begun yielding clues to the underlying mechanisms of pattern formation in the rodent somatosensory system, with profound implications for other sensory pathways in the mammalian brain. Current understanding is that topographically organized projections (somatotopic maps) along the somatosensory system are es...

Developmental and comparative aspects of posterior medial thalamocortical innervation of the barrel cortex in mice and rats

“…This is based principally on the observations that barrel centers are discernible cytoarchitecturally earlier than septa (Rice and Van der Loos, 1977) and that VPM TCAs are present within infragranular layers at birth and rapidly (within ~1–2 days) form whisker-related clusters (Wise and Jones, 1978; Erzurumlu and Jhaveri, 1990; Senft and Woolsey, 1991; Agmon et al, 1993; Schlaggar and O’Leary, 1994; Catalano et al, 1996; Rebsam et al, 2002). Our data demonstrate that POm TCAs are also well-represented within infragranular layers by birth in both rats and mice, in agreement with a previous study of POm TCAs in developing rats (Galazo et al, 2007), and exhibit single-fiber morphology and a laminar innervation pattern very similar to those reported for VPM axons (Catalano et al, 1996; Rebsam et al, 2002; Lee et al, 2005). Thus, at birth, both sets of TCAs from POm and VPM nuclei are present and extend equally into the barrel cortex, which dispels the notion that there is a major temporal disparity in the arrival and positioning of the two sets of axons at the beginning of postnatal life.…”

Regulation of spine morphology and spine density by NMDA receptor signaling in vivo

“…NMDAR loss in the cortical neurons of Emx-Cre mice was not analyzed for each layer specifically. In cortical NR1 KO animals with Emx-Cre, rudimentary patches of barrels are formed, which is because of a lack of selective arborization of thalamocortical axons in layer 4 (32,34). However, in Nex-Cre-induced NR1 nulls, barrels are completely absent (Fig.…”

Role of pre- and postsynaptic activity in thalamocortical axon branching

“…A recent study in which monocular deprivation was combined with silencing cortical activity has further suggested that correlations between pre-and postsynaptic activity play a dominant role in segregation of axon arbors (12). In accordance with this view, molecular machinery in pre-and postsynaptic sites has also been shown to affect arbor formation of TC axons in the somatosensory cortex (13)(14)(15). However, the relative role of pre-and postsynaptic activity in TC axon branching remains unclear.…”