Structural Basis for Map Formation in the Thalamocortical Pathway of the Barrelless Mouse

Abstract

Barrelless mice (BRL) homozygous for the BRL mutation that disrupts the gene coding for adenylyl cyclase type I on chromosome 11 lack spatial segregation of layer IV cortical cells and of the thalamocortical axons (TCAs) into barrel domains. Despite these morphological perturbations, a functional topographic map has been demonstrated. We reconstructed individual biocytin-injected TCAs from thalamus to barrel cortex in NOR (normal) and BRL mice to analyze to what extent the TCA arborization pattern and bouton distribution could explain the topographic representation of the whisker follicles. In BRL, the geometry of TCA is modified within layer IV as well as in infragranular layers. However, in both strains, the spatial distribution of TCA in layer IV reflects the spatial relationship of their cell bodies in the ventrobasal nucleus of the thalamus. The morphometric analysis revealed that TCAs of both strains have the same length, branch number, and number of axonal boutons in layer IV. However, in barrelless, the boutons are distributed within a larger tangential extent. Analysis of the distribution of boutons from neighboring thalamic neurons demonstrated the existence in layer IV of domains of high bouton density that in both strains equal the size and shape of individual barrels. We propose that the domains of high bouton density are at the basis of the whisker map in barrelless mice.

Neurotransmitter Release at the Thalamocortical Synapse Instructs Barrel Formation But Not Axon Patterning in the Somatosensory Cortex

“…This assumption was based on previous observations in mutants with defective presynaptic function (Laurent et al, 2002; Lu et al, 2006) and altered segregation of the TC axons. In MAOA KO (Cases et al, 1996; Rebsam et al, 2002) and AC1 KO mice (Welker et al, 1996; Gheorghita et al, 2006), TC axons invade the space between barrels. A proposed model for these changes was that TC afferents are selectively strengthened or destabilized based on their release probability (Lu et al, 2006).…”

“…The development of a barrel is initiated by the clustering of thalamocortical (TC) axon terminals, followed by an arrangement of the cortical layer IV neurons and by the orientation of their dendrites toward incoming TC terminal arborizations (Wu et al, 2011). The formation of barrels over the first postnatal week depends on neural activity, with the involvement of both presynaptic and postsynaptic mechanisms (Iwasato et al, 2000; Hannan et al, 2001; Rebsam et al, 2002; Gheorghita et al, 2006; Lu et al, 2006; Ballester-Rosado et al, 2010). …”

Synaptic Connections between Layer 5B Pyramidal Neurons in Mouse Somatosensory Cortex Are Independent of Apical Dendrite Bundling

“…6, 7, compare apical dendrite branching). The anatomical basis for barrel columns is the columnar geometry of thalamocortical projections (Jensen and Killackey, 1987;Gheorghita et al, 2006). Apical dendrites from L5B pyramidal cells in different bundles are well separated in layer 4, where they could be targeted by thalamocortical afferents that are restricted to a single bundle (Fig.…”

Modified Sensory Processing in the Barrel Cortex of the Adult Mouse After Chronic Whisker Stimulation

“…Additionally, a small proportion of layer IV axon collaterals to supragranular layers fans out to adjacent columns (Lübke et al 2000) and collaterals of the projections between supragranular and infragranular layers often terminate in adjacent columns (Bernardo et al 1990;Chagnac-Amitai et al 1990). Because of the paucity of direct interbarrel connections and the observations that layers II & III transcolumnar projections mainly avoid barrels (Brecht et al 2003;Lübke et al 2000;Petersen et al 2003b), it has been hypothesized that SW responses of layer IV barrel cells could originate from TC cells in the corresponding barreloid transmitting their SRF to the cortex (Brecht and Sakmann 2002b;Kwegyir-Afful et al 2005;Petersen and Sakmann 2001;Simons and Carvell 1989) or from divergent TC projections entering neighboring barrels (Arnold et al 2001;Gheorghita et al 2006;Keller and Carlson 1999;Land et al 1995). However, direct barrel-to-barrel connections were previously demonstrated at a functional level (Schubert et al 2003;Staiger et al 2004).…”