Watching synaptogenesis in the adult brain.

Although the lifelong addition of new neurons to the olfactory bulb and dentate gyrus of mammalian brains is by now an accepted fact, the function of adult-generated neurons still largely remains a mystery. The ability of new neurons to form synapses with preexisting neurons without disrupting circuit function is central to the hypothesized role of adult neurogenesis as a substrate for learning and memory. With the development of several new genetic labeling and imaging techniques, the study of synapse development and integration of these new neurons into mature circuits both in vitro and in vivo is rapidly advancing our insight into their structural plasticity. Investigators' observation of synaptogenesis occurring in the adult brain is beginning to shed light on the flexibility that adult neurogenesis offers to mature circuits and the potential contribution of the transient plasticity that new neurons provide toward circuit refinement and adaptation to changing environmental demands.

Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4.

Electrical activity regulates the manner in which neurons mature and form connections to each other. However, it remains unclear whether increased single-cell activity is sufficient to alter the development of synaptic connectivity of that neuron or whether a global increase in circuit activity is necessary. To address this question, we genetically increased neuronal excitability of in vivo individual adult-born neurons in the mouse dentate gyrus via expression of a voltage-gated bacterial sodium channel. We observed that increasing the excitability of new neurons in an otherwise unperturbed circuit leads to changes in both their input and axonal synapses. Furthermore, the activity-dependent transcription factor Npas4 is necessary for the changes in the input synapses of these neurons, but it is not involved in changes to their axonal synapses. Our results reveal that an increase in cell-intrinsic activity during maturation is sufficient to alter the synaptic connectivity of a neuron with the hippocampal circuit and that Npas4 is required for activity-dependent changes in input synapses.

Increasing heterogeneity in the organization of synaptic inputs of mature olfactory bulb neurons generated in newborn rats.

New neurons are added into the mammalian olfactory bulb throughout life, but it remains unknown whether the properties of new neurons generated in newborn animals differ from those added during adulthood. We compared the densities of glutamatergic synapses of granule cells (GCs) generated in newborn and adult rats over extended periods of time. We observed that, whereas adult-born GCs maintained stable cell-to-cell variability of synaptic densities soon after they integrated into the circuit, cell-to-cell variability of synaptic densities of neonatal-born GCs increased months after their integration. We also investigated whether the synaptic reorganization induced by sensory deprivation occurred differently in mature neonatal- and adult-born GCs. Sensory deprivation after new GCs had differentiated induced more pronounced changes in the synaptic densities of neonatal-born GCs than in adult-born GCs. These observations suggest that the synapses of mature neonatal-born GCs retain a higher degree of malleability in response to changes in neuronal activity than adult-born GCs.

Applications of avian transgenesis.

The ability to introduce foreign DNA into the genome of an organism has proven to be one of the most powerful tools in modern biology. Methods for the manipulation of the animal genome have been developed at an impressive pace for 3 decades, but only in the past 5 years have useful tools for avian transgenesis emerged. The most efficient technique involves the use of replication-deficient lentiviral vectors to deliver foreign DNA into the avian germline. Although lentiviral-mediated transgenesis presents some constraints, progress in this area has garnered interest in both industry and academia for its potential applications in biological research, biotechnology, and agriculture. In this review we evaluate methods for the production of transgenic birds, focusing on the advantages and limitations of lentiviral-mediated transgenesis. We also provide an overview of future applications of this technology. The most exciting of these include disease-resistant transgenic poultry, genetically modified hens that produce therapeutic proteins in their eggs, and transgenic songbirds that serve as a model to study communication disorders. Finally, we discuss technological advances that will be necessary to make avian transgenesis a more versatile tool.

Genetically increased cell-intrinsic excitability enhances neuronal integration into adult brain circuits.

New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits.