Diverse processing underlying frequency integration in midbrain neurons of barn owls.

Emergent response properties of sensory neurons depend on circuit connectivity and somatodendritic processing. Neurons of the barn owl's external nucleus of the inferior colliculus (ICx) display emergence of spatial selectivity. These neurons use interaural time difference (ITD) as a cue for the horizontal direction of sound sources.

Toric Spines at a Site of Learning.

We discovered a new type of dendritic spine. It is found on space-specific neurons in the barn owl inferior colliculus, a site of experience-dependent plasticity. Connectomic analysis revealed dendritic protrusions of unusual morphology including topological holes, hence termed "toric" spines ( = 76).

Hunting increases phosphorylation of calcium/calmodulin-dependent protein kinase type II in adult barn owls.

Juvenile barn owls readily adapt to prismatic spectacles, whereas adult owls living under standard aviary conditions do not. We previously demonstrated that phosphorylation of the cyclic-AMP response element-binding protein (CREB) provides a readout of the instructive signals that guide plasticity in juveniles. Here we investigated phosphorylation of calcium/calmodulin-dependent protein kinase II (pCaMKII) in both juveniles and adults.

Input clustering in the normal and learned circuits of adult barn owls.

Experience-dependent formation of synaptic input clusters can occur in juvenile brains. Whether this also occurs in adults is largely unknown. We previously reconstructed the normal and learned circuits of prism-adapted barn owls and found that changes in clustering of axo-dendritic contacts (putative synapses) predicted functional circuit strength.

Input clustering and the microscale structure of local circuits.

The recent development of powerful tools for high-throughput mapping of synaptic networks promises major advances in understanding brain function. One open question is how circuits integrate and store information. Competing models based on random vs.

Auditory processing, plasticity, and learning in the barn owl.

The human brain has accumulated many useful building blocks over its evolutionary history, and the best knowledge of these has often derived from experiments performed in animal species that display finely honed abilities. In this article we review a model system at the forefront of investigation into the neural bases of information processing, plasticity, and learning: the barn owl auditory localization pathway. In addition to the broadly applicable principles gleaned from three decades of work in this system, there are good reasons to believe that continued exploration of the owl brain will be invaluable for further advances in understanding of how neuronal networks give rise to behavior.

Bidirectional regulation of the cAMP response element binding protein encodes spatial map alignment in prism-adapting barn owls.

The barn owl midbrain contains mutually aligned maps of auditory and visual space. Throughout life, map alignment is maintained through the actions of an instructive signal that encodes the magnitude of auditory-visual mismatch. The intracellular signaling pathways activated by this signal are unknown.

Micro-rewiring as a substrate for learning.

How does the brain encode life experiences? Recent results derived from vital imaging, computational modeling, cellular physiology and systems neuroscience have pointed to local changes in synaptic connectivity as a powerful substrate, here termed micro-rewiring. To examine this hypothesis, I first review findings on micro-structural dynamics with focus on the extension and retraction of dendritic spines. Although these observations demonstrate a biological mechanism, they do not inform us of the specific changes in circuit configuration that might occur during learning.

Learning drives differential clustering of axodendritic contacts in the barn owl auditory system.

Computational models predict that experience-driven clustering of coactive synapses is a mechanism for information storage. This prediction has remained untested, because it is difficult to approach through time-lapse analysis. Here, we exploit a unique feature of the barn owl auditory localization pathway that permits retrospective analysis of prelearned and postlearned circuitry: owls reared wearing prismatic spectacles develop an adaptive microcircuit that coexists with the native one but can be analyzed independently based on topographic location.

Transcriptome changes associated with instructed learning in the barn owl auditory localization pathway.

Owls reared wearing prismatic spectacles learn to make adaptive orienting movements. This instructed learning depends on re-calibration of the midbrain auditory space map, which in turn involves the formation of new synapses. Here we investigated whether these processes are associated with differential gene expression, using longSAGE.

Axodendritic contacts onto calcium/calmodulin-dependent protein kinase type II-expressing neurons in the barn owl auditory space map.

In the owl midbrain, a map of auditory space is synthesized in the inferior colliculus (IC) and conveyed to the optic tectum (OT). Ascending auditory information courses through these structures via topographic axonal projections. Little is known about the molecular composition of projection neurons or their postsynaptic targets.

Multiple sites of adaptive plasticity in the owl's auditory localization pathway.

In the midbrain auditory localization pathway of the barn owl, a map of auditory space is relayed from the external nucleus of the inferior colliculus (ICX) to the deep and intermediate layers of the optic tectum (OT) and from these layers to the superficial layers. Within the OT, the auditory space map aligns with a visual map of space. Raising young barn owls with a prismatic displacement of the visual field leads to progressive changes in auditory tuning in the OT that tend to realign the auditory space map with the prismatically displaced visual space map.

Adaptive axonal remodeling in the midbrain auditory space map.

The auditory space map in the external nucleus of the inferior colliculus (ICX) of barn owls is highly plastic, especially during early life. When juvenile owls are reared with prismatic spectacles (prisms) that displace the visual field laterally, the auditory spatial tuning of neurons in the ICX adjusts adaptively to match the visual displacement. In the present study, we show that this functional plasticity is accompanied by axonal remodeling.

Traces of learning in the auditory localization pathway.

One of the fascinating properties of the central nervous system is its ability to learn: the ability to alter its functional properties adaptively as a consequence of the interactions of an animal with the environment. The auditory localization pathway provides an opportunity to observe such adaptive changes and to study the cellular mechanisms that underlie them. The midbrain localization pathway creates a multimodal map of space that represents the nervous system's associations of auditory cues with locations in visual space.

Proteins involved in synaptic vesicle trafficking.

Neurotransmitter release relies on a series of synaptic vesicle trafficking reactions. We have determined the molecular basis of these reactions by microinjecting, into 'giant' nerve terminals of squid, probes that interfere with presynaptic proteins. These probes affect neurotransmitter release and disrupt nerve terminal structure.

Protein interactions implicated in neurotransmitter release.

Biochemical evidence indicates that the exocytotic release of neurotransmitters involves both evolutionary conserved membrane proteins, the SNAREs, as well as ubiquitous cytosolic fusion proteins, NSF and SNAPs. We have analyzed the biochemical properties and the physiological effects of these proteins. Our data suggest models how NSF, SNAPs and SNAREs may function in neurotransmitter exocytosis.

A neuronal Sec1 homolog regulates neurotransmitter release at the squid giant synapse.

Sec1-related proteins are essential for membrane fusion at distinct stages of the constitutive and regulated secretory pathways in eukaryotic cells. Studies of neuronal isoforms of the Sec1 protein family have yielded evidence for both positive and negative regulatory functions of these proteins in neurotransmitter release. Here, we have identified a squid neuronal homolog (s-Sec1) of Sec1 proteins and examined its function in neurotransmitter release at the squid giant synapse.

Regulation of neurotransmitter release kinetics by NSF.

NSF (N-ethylmaleimide-sensitive factor) is an adenosine triphosphatase (ATPase) that contributes to a protein complex essential for membrane fusion. The synaptic function of this protein was investigated by injecting, into the giant presynaptic terminal of squid, peptides that inhibit the ATPase activity of NSF stimulated by the soluble NSF attachment protein (SNAP). These peptides reduced the amount and slowed the kinetics of neurotransmitter release as a result of actions that required vesicle turnover and occurred at a step subsequent to vesicle docking.

Exocytosis: proteins and perturbations.

Exocytosis is the primary means of cellular secretion. Because exocytosis involves fusion between the plasma membrane and the membrane of secretory vesicles, it is likely that proteins on these two membranes, as well as additional proteins in cellular cytoplasm, mediate exocytosis. Although we know much about the proteins of secretory cells, we still have much to learn about how these proteins participate in exocytosis; in no case has an unambiguous exocytotic function been assigned to any of these proteins.

SNAP-mediated protein-protein interactions essential for neurotransmitter release.

The constitutive fusion of transport vesicles with intracellular membranes requires soluble proteins called SNAPs. Certain presynaptic proteins implicated in synaptic vesicle exocytosis also bind SNAPs, suggesting that SNAPs participate in the calcium-regulated membrane fusion events mediating neurotransmitter release. Here we show that injection of recombinant SNAPs into the giant synapse of squid enhances transmitter release.

Molecular pathways for presynaptic calcium signaling.

The results presented in this article describe two distinct, Ca-regulated molecular pathways in presynaptic terminals and implicate these two pathways in differentially mediating neurotransmitter secretion and PTP. Our current view of the Ca-dependent triggering of secretion and PTP is shown in Fig. 9.