A model was developed to examine dynamical properties of regulatory motifs correlated with different temporal domains of memory. The model represents short-, intermediate-, and long-term phases of protein kinase A (PKA) activation, which appear related to corresponding phases of facilitation of the Aplysia sensorimotor synapse. The model also represents phosphorylation of the transcription factor CREB1 by PKA and consequent induction of the immediate-early gene Aplysia ubiquitin hydrolase (Ap-uch), which is essential for long-term synaptic facilitation (LTF). Simulations suggest mechanisms responsible for differing profiles of synaptic facilitation following massed vs. spaced exposures to 5-HT, and suggest a novel regulatory motif (gated positive feedback) is important for LTF. Simulations suggest zero-order ultrasensitivity may underlie a requirement of a threshold number of exposures to 5-HT for LTF induction. The model makes predictions for the dynamics of PKA activation and Ap-uch induction when MAP kinase is activated, or when repression of Ap-uch is relieved by inhibiting the transcription factor CREB2. This model may therefore be useful for understanding processes underlying memory formation in Aplysia and other systems.

Cervical lordosis and kyphosis less than +7.5° resulted in no meaningful increase in IMP. Minor cervical kyphosis measuring +7.5° to +21° resulted in 2 to 5 mm Hg increases in IMP. As the cervical kyphotic deformity exceeded +21°, IMP increased significantly. ΔIMP with spinal alignment may help to explain the wide range of "normal" cervical neutral upright sagittal alignment in studies of asymptomatic individuals and may help further define cervical kyphotic deformity.

A refined battery of neurological tests, SNAP (Simple Neuroassessment of Asymmetric Impairment), was developed and validated to efficiently assess neurological deficits induced in a mouse model of traumatic brain injury. Four to 7-month old mice were subjected to unilateral controlled cortical impact or sham injury (craniectomy only). Several behavioral tests (SNAP, beam walk, foot fault, and water maze) were used to assess functional deficits. SNAP was unique among these in that it required no expensive equipment and was performed in less than 5 min per mouse. SNAP demonstrated a high level of sensitivity and specificity as determined by receiver-operator characteristics curve analysis. Interrater reliability was good, as determined by Cohen's Kappa method and by comparing the sensitivity and specificity across various raters. SNAP detected deficits in proprioception, visual fields, and motor strength in brain-injured mice at 3 days, and was sensitive enough to detect magnitude and recovery of injury. The contribution of individual battery components changed as a function of time after injury, however, each was important to the overall SNAP score. SNAP provided a sensitive, reliable, time-efficient and cost-effective means of assessing neurological deficits in mice after unilateral brain injury.

Axonal regeneration is normally limited within myelinated fiber tracts in the CNS of higher vertebrates. Numerous studies suggest that CNS myelin contains inhibitors that may contribute to abortive axonal growth. In contrast to the evidence of myelin-associated neurite inhibitors, embryonic neurons transplanted into the CNS can regenerate extensively within myelinated tracts in vivo. It has been speculated that embryonic neurons do not yet express the appropriate receptors for myelin-associated inhibitors. Recently, however, extensive regeneration from transplanted adult neurons has also been reported within myelinated tracts of the CNS, casting doubt on the role myelin-associated inhibitors play in abortive regeneration. The present study reexamined the potential of white matter to support neurite growth in vitro. By the use of Neurobasal medium, neurons were cultured onto unfixed cryostat sections of mature rat CNS tissue. As documented previously, robust neuronal attachment and neurite outgrowth occurred on gray matter but these neurites were sharply inhibited by white matter. In addition, however, increased rates of neuronal attachment directly to white matter occurred with neurite outgrowth comparable in length with that on gray matter but limited to directions parallel to the fiber tract. Frequently, the same section of white matter was found to inhibit neurite outgrowth from neurons on gray matter while supporting parallel neurite outgrowth from neurons on white matter. These results suggest that whether white matter supports or inhibits axonal growth depends on the geometric relationship between the axon and the fiber tract; more specifically, white matter supports parallel growth but inhibits nonparallel growth.