Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder.

Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition. Expression of c-fos was increased in cortical pyramidal neurons, consistent with increased neuronal activity due to disinhibition. The mice showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by antimania drugs lithium and valproate. Repeated social defeat stress resulted in repeated episodes of dramatic behavioral changes from hyperactivity to "depression-like" behavior, suggestive of some aspects of human bipolar disorder. Overall, we suggest that this Ank-G cKO mouse model recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. The model may be useful for studying disease pathophysiology and for developing experimental therapeutics.

Finding Home: A Qualitative Approach to Understanding Adolescent Mothers' Housing Instability.

Many low-income Latina adolescent mothers face instability in their housing circumstances, which has implications for their long-term prospects and that of their children. This study used longitudinal, ethnographic data from Welfare, Children, and Families: A Three-City Study to explore experiences of low-income, Latina adolescent mothers (N = 15) with unstable housing who primarily rely on their families or the families of their significant others for housing support. Results of analysis employing grounded theory and narrative approaches suggested two types of instability: "Horizontal moves" between family homes and "vertical moves" between family homes and independent living. Although family support often was fundamental in allowing for participants' pursuit of independent housing (i.e., vertical moves), it also was associated with greater residential mobility (i.e., horizontal moves), most often in the context of intrafamilial conflict and family instability. These results are discussed with respect to inconsistencies in policies to address this vulnerable population.

Does poor health predict moving, move quality, and desire to move?: A study examining neighborhood selection in US adolescents and adults.

To date, research has rarely considered the role of health in shaping characteristics of the neighborhood, including mobility patterns. We explored whether individual health status shapes and constrains where individuals live. Using the National Longitudinal Study of Adolescent Health data, we examined whether 16 health indicators predicted moving, move quality, and desire to move. 3.8% of adolescents (n=490) reported a move in the past year. In the unadjusted models, 10 health indicators were associated with moving; the magnitude of association for these health indicators was similar to socio-demographic characteristics. 7 of these health-moving associations persisted after adjusting for covariates. Health was also associated with moving quality, with a greater number of past year health problems in the child being associated with moving to a lower income neighborhood and parent disability or poor health being associated with moving to a higher income neighborhood. Almost every poor health status indicator was associated with a greater desire to move. Findings suggest that health status influences moving, and a reciprocal framework is more appropriate for examining health-neighborhood linkages.

Long-term modification of cortical synapses improves sensory perception.

Synapses and receptive fields of the cerebral cortex are plastic. However, changes to specific inputs must be coordinated within neural networks to ensure that excitability and feature selectivity are appropriately configured for perception of the sensory environment. We induced long-lasting enhancements and decrements to excitatory synaptic strength in rat primary auditory cortex by pairing acoustic stimuli with activation of the nucleus basalis neuromodulatory system. Here we report that these synaptic modifications were approximately balanced across individual receptive fields, conserving mean excitation while reducing overall response variability. Decreased response variability should increase detection and recognition of near-threshold or previously imperceptible stimuli. We confirmed both of these hypotheses in behaving animals. Thus, modification of cortical inputs leads to wide-scale synaptic changes, which are related to improved sensory perception and enhanced behavioral performance.