Research
Our lab focuses on basic mechanisms of neural development, learning, and memory. Our goal is to elucidate mechanisms that regulate basic processes of neural development, and in so doing to shed light on factors governing the emergence of a learned behavior. These studies are yielding basic information regarding synaptic plasticity and learning, as well as factors that regulate fundamental processes of neural development. The results are therefore highly relevant to questions of normal brain function, especially the enhanced learning capacity of juvenile brains, as well as to the brain’s response to injury, disease and aging. On-going projects include the role of neurotrophic growth factors in preventing neurodegeneration so as to sculpt neural circuits for vocal learning, the influence of sensory experience and growth factors in regulating morphology of axons and the specificity of their connections, and changes in synaptic strength in vocal-control circuits during learning that are induced by experience and resultant changes in neural activity and the expression of specific molecules such as NMDA receptors.

For example, Allison Quaglino is studying how the neurotrophin family of growth factors regulates neuron survival in RA, the cortical brain region that controls motor production of vocal behavior. Past work in the lab has shown that pre-synaptic axons from lMAN are necessary to support the survival of RA neurons in 20-day old birds at the onset of song learning. Allison’s thesis project will test how pre-synaptic lMAN inputs to RA regulate growth factors such as BDNF and NT-3 to prevent the death of RA neurons. Read more...

Haruhusa Okawa is studying the effects of the neurotrophin family of growth factors on the neurophysiology of song-control neurons. He is following up on work done in mammalian brain showing that BDNF can elicit extremely rapid depolarization of neurons – that is BDNF can act as a potent excitatory neurotransmitter. His initial work has shown that applying BDNF to lMAN in brain slices causes neurons to fire a train of action potentials. One idea is that BDNF is released at synapses to cause a strong depolarization. Read more...

Michael Grammer is studying developmental changes in NMDA receptors during vocal learning. In order to be activated, NMDA receptors require both a ligand-binding signal (provided by release of glutamate from pre-synaptic axons), and also require that the post-synaptic cell be de-polarized (caused by correlated activity of many pre-synaptic inputs, for example). He has found that many synapses on lMAN neurons have synapses that contain only NMDA receptors. We believe such synapses may act as a selective filter that gate through only highly correlated patterns of information, such as auditory and motor feedback that match the tutor song that the bird is learning to copy. Read more...

Brie Altenau is testing structure-function relationships of brain regions involved in vocal learning. Past work in the lab has shown that lMAN is composed of two different sub-divisions: a core of mostly large neurons and a surrounding shell of large and small neurons. The axonal connections of the core and shell sub-divisions form independent neural pathways that traverse the forebrain in parallel. Brie is lesioning the shell pathway and then studying the resultant disruption in song behavior. We think the shell pathway may be important during early stages of song learning for evaluating the degree of error between the vocal sounds the bird actually produces with the tutor song sounds he is trying to produce. Read more...

Another project in the lab focuses on the morphology of individual axon terminals and how axonal connections between different brain regions achieve the specificity required to encode a specific song pattern during development. For example, Soumya Iyengar showed that the projection from lMAN to RA was exuberant at the onset of the sensitive period for vocal learning in 20-day old birds, and that these axons regressed substantially by 35 days to create the adult pattern of organizational specificity in this pathway. Thus, it is interesting that lMAN inputs to RA are greatest in number at the onset of song learning, when RA neurons are dependent on these inputs for survival. By 40 days, lMAN axons have regressed, and RA neurons no longer require pre-synaptic contact from these axons to survive. Future experiments will study how growth factors influence neuron survival, axon re-modeling, and the development of learned vocal behavior. Read more...

For more information on projects in the lab, read the additional descriptions of Past Lab Members.



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The Sarah W. Bottjer Laboratory, Hedco Neuroscience Building, University Park Campus , Los Angeles, CA., 90089