Postcranial skeletal pneumaticity in non-aquatic neoavians: Insights from accipitrimorphae.

Postcranial skeletal pneumaticity, air-filled bones of the trunk and limbs, is exclusive to birds among extant tetrapods and exhibits significant variation in its expression among different species. Such variation is not random but exhibits relationships with both body mass and locomotor specializations. Most species-level comparative research to date has focused on aquatic-oriented taxa (e.g., Anseriformes). The lack of data from non-aquatic birds constrains our ability to characterize global (i.e., avian-wide) patterns of this trait complex. To address this gap, the study conducted herein quantified postcranial pneumaticity in Accipitrimorphae, a mostly terrestrial clade composed of species that span a range of body sizes and exhibit diverse flight/foraging behaviors. All examined species (n = 88) invariably pneumatized the postaxial through pre-caudal vertebrae, sternum, coracoid, humerus, vertebral and sternal ribs, and pelvic girdle, a pattern herein referred to as the accipitrimorph baseline. Of the 88 sampled species, 41 expanded upon this pattern, whereas 10 species exhibited a reduction. No species deviated from the accipitrimorph baseline by more than two anatomical regions. A phylogenetically-informed regression analysis failed to identify a significant relationship between body mass and pneumaticity. However, specific pneumaticity phenotypes deviating from the baseline were correlated with aspects of wing morphology, tail length, and home range size. Results from this and previous studies provide clarity on two hypotheses: (1) aquatic taxa display distinct pneumaticity expression patterns relative to non-aquatic birds, notably with reductions in the proportion of the skeleton filled with air in diving specialists and (2) contemporary comparative studies, including the one herein, that explicitly account for phylogenetic relationships consistently fail to support the oft-cited positive relationship between pneumaticity and body mass. Instead, historical relationships and functional/ecological attributes (e.g., diving, specialized flight behaviors) appear to be the primary drivers underlying patterns of variation in this trait complex.

Postcranial Skeletal Pneumaticity in Cuculidae.

Postcranial skeletal pneumaticity (i.e., epithelial-lined, air-filled bones) is a condition unique to birds among extant tetrapods. Previous research reveals extensive variation in the expression of this trait in different bird species, from taxa that pneumatize nearly the entire skeleton to others that do not pneumatize a single bone. These studies, however, have primarily focused on aquatic/semi-aquatic birds, specifically Anseriformes (screamers, ducks, geese, swans) and Aequorlitornithes (loons, gulls, penguins, storks, etc.). This is the first clade-centric study of pneumaticity in an exclusively terrestrial clade (i.e., a group without any proclivities for water), Cuculidae. Given the variation in body size and ecology exhibited by cuckoos, they represent an ideal group for evaluating previously established trends in pneumaticity patterns. Similar to previous studies, our results indicate that cuckoos do exhibit extensive postcranial skeletal pneumaticity but with much more limited variation in expression. Of the surveyed species, 30 of 41 display an identical expression pattern, pneumatizing all postaxial vertebrae, the humerus, sternum, and pelvic girdle. The remaining species (11/41) deviate from this pattern by no more than two elements (i.e., the femur or the scapula/coracoid). All variable species expand upon the basic cuckoo pattern, with five species pneumatizing the femur and the remaining six taxa pneumatizing both the scapula and coracoid. Furthermore, most variation occurs in early diverging clades, with distinct subclades associated with specific anatomical expansions in pneumaticity (e.g., pneumatic femora in Neomorphinae and pneumatic scapulae/coracoids in select members of Couinae and Centropodinae). Limited variation noted in Cuculidae may be the result of the relatively high base level of pneumaticity when compared with previously sampled groups of water-oriented birds. Additional analyses indicate a positive relationship between body mass and pneumaticity, with possible (i.e., non-quantifiable) relationships noted between the limited expansions from the basic cuckoo pattern and specific locomotor behaviors (e.g., pneumatic femora present in species with enhanced cursorial behavior). These basic trends have also been observed in other densely sampled neognath clades. Taken together, the data presented herein supports the hypothesis that changes in pneumaticity expression may be correlated with shifts in biomechanical loading regimes rather than solely as a weight saving (i.e., density-altering) mechanism.

Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-ß-carboline-3-carboxylate) in neonatal rats.

Levetiracetam (LEV) and tiagabine (TGB) are utilized for the treatment of seizures, including neonatal seizures. However, relatively little is known about the preclinical therapeutic profile of these drugs during brain development. The relative paucity of information regarding these drugs in neonatal animals may be due to their unusual profile of anticonvulsant action in experimental models. LEV and TGB are without effect against seizures in several common screening models (e.g., the maximal electroshock test, maximal pentylenetetrazole seizures), instead showing preferential efficacy against models of partial seizures. We have recently described a method for reliably evoking partial seizures in neonatal animals by systemic administration of the chemoconvulsant, DMCM (Kulick et al., 2014, Eur. J. Pharmacol., doi:10.1016/j.ejphar.2014.06.012). DMCM is a negative allosteric modulator of GABAA receptors, and offers a wide separation between doses required to evoke complex partial as compared to tonic-clonic seizures. Here we used DMCM to evaluate the effect of LEV and TGB against seizures in postnatal day (P) 10 rat pups. We compared the profile of LEV and TGB to that of phenobarbital (PB), the most widely utilized anticonvulsant in neonates. We found that LEV significantly protected against DMCM seizures when administered in doses of 10mg/kg and greater. TGB protected against DMCM-evoked seizures when administered in doses of 1mg/kg or greater. PB protected against DMCM-evoked seizures when administered in doses of 5mg/kg or greater. These data provide preclinical evidence for the efficacy of LEV and TGB in neonates and underscore the utility of DMCM for screening anticonvulsant action in neonatal animals.

Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.

Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital.