Mice homozygous for the barrelless (brl) mutation, mapped here to chromosome 11, lack barrel-shaped arrays of cell clusters termed "barrels" in the primary somatosensory cortex. Deoxyglucose uptake demonstrated that the topology of the cortical whisker representation is nevertheless preserved. Anterograde tracers revealed a lack of spatial segregation of thalamic afferents into individual barrel territories, and single-cell recordings demonstrated a lack of temporal discrimination of center from surround information. Thus, structural segregation of thalamic inputs is not essential to generate topological order in the somatosensory cortex, but it is required for discrete spatiotemporal relay of sensory information to the cortex.

Cortical map formation requires the accurate targeting, synaptogenesis, elaboration and refinement of thalamocortical afferents. Here we demonstrate the role of Ca2+/calmodulin-activated type-I adenylyl cyclase (AC1) in regulating the strength of thalamocortical synapses through modulation of AMPA receptor (AMPAR) trafficking using barrelless mice, a mutant without AC1 activity or cortical 'barrel' maps. Barrelless synapses are stuck in an immature state that contains few functional AMPARs that are rarely silent (NMDAR-only). Long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical synapses require postsynaptic protein kinase A (PKA) activity and are difficult to induce in barrelless mice, probably due to an inability to properly regulate synaptic AMPAR trafficking. Consistent with this, both the extent of PKA phosphorylation on AMPAR subunit GluR1 and the expression of surface GluR1 are reduced in barrelless neurons. These results suggest that activity-dependent mechanisms operate through an AC1/PKA signaling pathway to target some synapses for consolidation and others for elimination during barrel map formation.

Rocker (gene symbol rkr), a new neurological mutant phenotype, was found in descendents of a chemically mutagenized male mouse. Mutant mice display an ataxic, unstable gait accompanied by an intention tremor, typical of cerebellar dysfunction. These mice are fertile and appear to have a normal life span. Segregation analysis reveals rocker to be an autosomal recessive trait. The overall cytoarchitecture of the young adult brain appears normal, including its gross cerebellar morphology. Golgi-Cox staining, however, reveals dendritic abnormalities in the mature cerebellar cortex characterized by a reduction of branching in the Purkinje cell dendritic arbor and a "weeping willow" appearance of the secondary branches. Using simple sequence length polymorphism markers, the rocker locus was mapped to mouse chromosome 8 within 2 centimorgans of the calcium channel alpha1a subunit (Cacna1a, formerly known as tottering) locus. Complementation tests with the leaner mutant allele (Cacna1a(la)) produced mutant animals, thus identifying rocker as a new allele of Cacna1a (Cacna1a(rkr)). Sequence analysis of the cDNA revealed rocker to be a point mutation resulting in an amino acid exchange: T1310K between transmembrane regions 5 and 6 in the third homologous domain. Important distinctions between rocker and the previously characterized alleles of this locus include the absence of aberrant tyrosine hydroxylase expression in Purkinje cells and the separation of the absence seizures (spike/wave type discharges) from the paroxysmal dyskinesia phenotype. Overall these findings point to an important dissociation between the seizure phenotypes and the abnormalities in catecholamine metabolism, and they emphasize the value of allelic series in the study of gene function.

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