Structural and functional differences in the barrel cortex of Mecp2 null mice
Mecp2 is X‐linked and mutant homozygous female mice do not survive; males carrying the mutation (−/y) survive and are considered Mecp2‐null. Mecp2 null mice exhibit several characteristics of RTT at 3–8 weeks of age, while heterozygous female mice exhibit some of the characteristics of RTT after 6 months. Several research groups have generated Mecp2 mutant mouse lines. The initial constitutive Mecp2 deletion resulted in embryonic lethality (Tate, Skarnes, & Bird, 1996). Adrian Bird's laboratory circumvented embryonic lethality by conditional gene deletion approach. The resultant mouse line is known as the Bird model (Guy, Hendrich, Holmes, Martin, & Bird, 2001). Breeding Mecp2 heterozygous (Mecp2+/−) females with C57BL/6 males yield heterozygous females and hemizygous (Mecp2−/y) males; hemizygous males do not breed.
In many neurodevelopmental disorders, such as RTT, sensory processing deficits are common. A conspicuous behavioral stereotypy in children with RTT is hand to mouth kneading movements, which has both tactile sensory and motor components. In the human primary somatosensory cortex, proportionately largest areas are devoted to the hands and mouth. Likewise, in the mouse primary somatosensory cortex, a very large area is devoted to the representation of the facial whiskers. In fact, each whisker has a distinct, corresponding neural module known as a “barrel” because of the arrangement of layer IV neurons in a cylindrical array, with its center (hollow) filled by the discrete terminal arbors of thalamocortical axon (TCA) arbors corresponding to single whiskers (Agmon, Yang, Jones, & O'Dowd, 1995; Lee, Iwasato, Itohara, & Erzurumlu, 2005; Rebsam, Seif, & Gaspar, 2002; Senft & Woolsey, 1991; Woolsey & Van der Loos, 1970). Thus, the whisker‐barrel pathway of mice provides a unique model to study sensory processing defects in mutant mouse models of neurodevelopmental disorders.
In this study, we investigated peripherally evoked sensory activity in the barrel cortex of male Mecp2 null mice and present analysis of the morphological differentiation of TCA terminals and dendrites of the barrel cells that receive peripherally evoked activity through them.