Noradrenergic induction of odor-specific neural habituation and olfactory memories.

For many mammals, individual recognition of conspecifics relies on olfactory cues. Certain individual recognition memories are thought to be stored when conspecific odor cues coincide with surges of noradrenaline (NA) triggered by intensely arousing social events. Such familiar stimuli elicit reduced behavioral responses, a change likely related to NA-dependent plasticity in the olfactory bulb (OB).

Genetic control of neuronal activity in mice conditionally expressing TRPV1.

Here we describe a knock-in mouse model for Cre-loxP-based conditional expression of TRPV1 in central nervous system neurons. Expression of Cre recombinase using biolistics, lentivirus or genetic intercrosses triggered heterologous expression of TRPV1 in a cell-specific manner. Application of the TRPV1 ligand capsaicin induced strong inward currents, triggered action potentials and activated stereotyped behaviors, allowing cell type-specific chemical genetic control of neuronal activity in vitro and in vivo.

Sparse and selective odor coding by mitral/tufted neurons in the main olfactory bulb.

The mammalian olfactory system recognizes an enormous variety of odorants carrying a wide range of important behavioral cues. In the main olfactory bulb (MOB), odorants are ultimately represented through the action potential activity of mitral/tufted cells (M/Ts), whose selectivity and tuning to odorant molecules are therefore fundamental determinants of MOB sensory coding. However, the sheer number and diversity of discrete olfactory stimuli has been a major barrier to comprehensively evaluating M/T selectivity.

Synaptic integration of olfactory information in mouse anterior olfactory nucleus.

Individual odorants activate only a small fraction of mitral cells in the mouse main olfactory bulb (MOB). Odor mixtures are represented by a combination of activated mitral cells, forming reproducible activation maps in the olfactory bulb. However, how the activation of a cohort of narrowly tuned mitral cells by odor mixtures is read out synaptically by neurons in higher-level olfactory structures, such as the anterior olfactory nucleus (AON), is mostly unknown.

Representation of natural stimuli in the rodent main olfactory bulb.

Natural odorants are complex mixtures of diverse chemical compounds. Monomolecular odorants are represented in the main olfactory bulb by distinct spatial patterns of activated glomeruli. However, it remains unclear how individual compounds contribute to population representations of natural stimuli, which appear to be unexpectedly sparse.

In vivo imaging of juxtaglomerular neuron turnover in the mouse olfactory bulb.

As a consequence of adult neurogenesis, the olfactory bulb (OB) receives a continuous influx of newborn neurons well into adulthood. However, their rates of generation and turnover, the factors controlling their survival, and how newborn neurons intercalate into adult circuits are largely unknown. To visualize the dynamics of adult neurogenesis, we produced a line of transgenic mice expressing GFP in approximately 70% of juxtaglomerular neurons (JGNs), a population that undergoes adult neurogenesis.

Encoding social signals in the mouse main olfactory bulb.

Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells.

Molecular organization of the ferret visual thalamus.

The visual system encodes and deciphers information using parallel, anatomically segregated, processing streams. To reveal patterns of gene expression in the visual thalamus correlated with physiological processing streams, we designed a custom ferret cDNA microarray. By isolating specific subregions and layers of the thalamus, we identified a set of transcription factors, including Zic2, Islet1, and Six3, the unique distribution profiles of which differentiated the lateral geniculate nucleus (LGN) from the associated perigeniculate nucleus.

An imaging-based approach to identify ligands for olfactory receptors.

Odorant receptors (ORs) form one of the largest gene families in the genome. However, the vast majority are orphan receptors as the ligands that activate them remain unknown. Deorphaning approaches have generally focused on finding ligands for particular receptors expressed in homologous or heterologous cells; these attempts have met with only partial success.

Encoding pheromonal signals in the mammalian vomeronasal system.

The past few years have delivered substantial progress in understanding the molecular logic of the mammalian vomeronasal system. Selective expression of vomeronasal receptors and high response selectivity of vomeronasal receptor neurons suggest that pheromones are encoded by labeled lines at the level of the vomeronasal organ: each pheromonal compound is represented by the activation of a small and exclusive subset of receptor neurons. Labeled lines might be transferred to the accessory olfactory bulb through convergent connections.

High-resolution in vivo imaging of hippocampal dendrites and spines.

Structural changes in hippocampal dendrites and dendritic spines are thought to be a consequence of a wide range of experience- and activity-dependent manipulations. We explored the dynamics of hippocampal dendritic spines in vivo by developing a surgical preparation of the adult mouse brain that enabled two-photon imaging of fluorescently labeled CA1 pyramidal neurons. Dendritic trees and spines were repeatedly visualized over many hours in exquisite detail.

Dendritic stability in the adult olfactory bulb.

In many regions of the adult mammalian brain, pronounced changes in synaptic input caused by lesions or severe sensory deprivation induce marked sprouting or retraction of neuronal dendrites. In the adult olfactory bulb, adult neurogenesis produces less pronounced, but continuously ongoing synapse turnover. To test the structural stability of adult dendrites in this context, we used two-photon microscopy to image dendrites of mitral and tufted (M/T) cells over prolonged periods in adult mice.

Functional topography of connections linking mirror-symmetric maps in the mouse olfactory bulb.

In rodents, each main olfactory bulb contains two mirror-symmetric glomerular maps, a feature not found in the initial topographic maps of other sensory systems. Targeting tracer injections to identified glomeruli revealed that isofunctional odor columns-translaminar assemblies connected to a given glomerulus-were specifically and reciprocally interconnected through a mutually inhibitory circuit with exquisite topographic specificity. Thus, instead of containing two mirror-symmetric maps, we propose that the olfactory bulb contains a single integrated map in which isofunctional odor columns are connected through an intrabulbar link, analogous to the specific horizontal connections linking iso-orientation columns in primary visual cortex.

Encoding pheromonal signals in the accessory olfactory bulb of behaving mice.

Many mammalian species rely on pheromones-semiochemicals produced by other members of the same species-to communicate social status and reproductive readiness. To assess how the central nervous system integrates the complex repertoire of pheromones, we recorded from single neurons in the accessory olfactory bulb, a nucleus that processes pheromonal signals, of male mice engaged in natural behaviors. Neuronal firing was robustly modulated by physical contact with male and female conspecifics, with individual neurons activated selectively by specific combinations of the sex and strain of conspecifics.

Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials.

Spatiotemporal patterns of excitation and inhibition evoked by the horizontal network in layer 2/3 of ferret visual cortex.

The horizontal network in visual cortex layer 2/3 is implicated in numerous psychophysical and physiological properties. To investigate the spatial and temporal distribution of excitation and inhibition evoked by this network, we used voltage-sensitive dyes to image the responses to focal electrical stimulation in tangential slices of ferret visual cortex layer 2/3. The resulting optical patterns included a diffuse zone of activation near the stimulation site and numerous ovoid domains throughout the slice.

BDNF release from single cells elicits local dendritic growth in nearby neurons.

In cultured neurons, the exogenous application of neurotrophins (in homogenous concentrations) alters many features of axonal and dendritic arbors. In vivo, however, release of endogenous neurotrophins from neuronal processes creates spatially heterogeneous neurotrophin distributions. To probe the consequences of such endogenous neurotrophin distribution, we produced 'donor neurons' in ferret cortex brain slices that co-expressed brain-derived neurotrophic factor (BDNF) and red fluorescent protein (RFP).

Odorant receptors instruct functional circuitry in the mouse olfactory bulb.

The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 --> M71, in which a functionally characterized receptor, rI7, has been substituted into the M71 receptor locus.

Ocular dominance development revisited.

New approaches to the study of ocular dominance development, a model system for the development of neural architecture, indicate that eye-specific columns in primary visual cortex emerge substantially before the onset of the critical period, during which neural connections can be altered by visual experience. The timing, speed and specificity of column emergence implicate molecular patterning mechanisms, along with patterns of neural activity, in the generation of this columnar architecture.

Development of cortical circuits: lessons from ocular dominance columns.

The development of ocular dominance columns has served as a Rosetta stone for understanding the mechanisms that guide the construction of cortical circuits. Traditionally, the emergence of ocular dominance columns was thought to be closely tied to the critical period, during which columnar architecture is highly susceptible to alterations in visual input. However, recent findings in cats, monkeys and ferrets indicate that columns develop far earlier, more rapidly and with considerably greater precision than was previously suspected.

Specificity in the Development of Vertical Connections in Cat Striate Cortex.

The main efferent axons of pyramidal cells in layer 2/3 in the adult cat striate cortex make collateral connections specifically within layer 2/3 and layer 5 and avoid the intervening layer 4. Intracellular dye injections in vitro were used to determine how, during early postnatal development, this precise pattern of laminar connections was achieved. These investigations revealed that the pattern of collateral outgrowth was specific from the very earliest time that axons began sprouting collaterals.