Research Interests: Systems Neuroscience
Overview: Dr. Smear studies the neural mechanisms of olfactory function in mice. Mice have an excellent sense of smell – much of their genome encodes odorant receptors (over 1000 genes), and a large portion of their brain processes olfactory information. These neural features support a rich repertoire of olfactory behaviors. The Smear lab interrogates olfactory function with a battery of psychophysical tests, while manipulating and recording neuronal activity with genetics, electrophysiology, and imaging. From these studies, the lab will pursue general principles of how neural circuits generate behavior.
RECENT PUBLICATIONS
Algorithms for Olfactory Search across Species.
J Neurosci. 2018 Oct 31;38(44):9383-9389
Authors: Baker KL, Dickinson M, Findley TM, Gire DH, Louis M, Suver MP, Verhagen JV, Nagel KI, Smear MC
Abstract
Localizing the sources of stimuli is essential. Most organisms cannot eat, mate, or escape without knowing where the relevant stimuli originate. For many, if not most, animals, olfaction plays an essential role in search. While microorganismal chemotaxis is relatively well understood, in larger animals the algorithms and mechanisms of olfactory search remain mysterious. In this symposium, we will present recent advances in our understanding of olfactory search in flies and rodents. Despite their different sizes and behaviors, both species must solve similar problems, including meeting the challenges of turbulent airflow, sampling the environment to optimize olfactory information, and incorporating odor information into broader navigational systems.
PMID: 30381430 [PubMed - in process]
Hierarchy of orofacial rhythms revealed through whisking and breathing.
Nature. 2013 May 09;497(7448):205-10
Authors: Moore JD, Deschênes M, Furuta T, Huber D, Smear MC, Demers M, Kleinfeld D
Abstract
Whisking and sniffing are predominant aspects of exploratory behaviour in rodents. Yet the neural mechanisms that generate and coordinate these and other orofacial motor patterns remain largely uncharacterized. Here we use anatomical, behavioural, electrophysiological and pharmacological tools to show that whisking and sniffing are coordinated by respiratory centres in the ventral medulla. We delineate a distinct region in the ventral medulla that provides rhythmic input to the facial motor neurons that drive protraction of the vibrissae. Neuronal output from this region is reset at each inspiration by direct input from the pre-Bötzinger complex, such that high-frequency sniffing has a one-to-one relationship with whisking, whereas basal respiration is accompanied by intervening whisks that occur between breaths. We conjecture that the respiratory nuclei, which project to other premotor regions for oral and facial control, function as a master clock for behaviours that coordinate with breathing.
PMID: 23624373 [PubMed - indexed for MEDLINE]
Precise olfactory responses tile the sniff cycle.
Nat Neurosci. 2011 Jul 17;14(8):1039-44
Authors: Shusterman R, Smear MC, Koulakov AA, Rinberg D
Abstract
In terrestrial vertebrates, sniffing controls odorant access to receptors, and therefore sets the timescale of olfactory stimuli. We found that odorants evoked precisely sniff-locked activity in mitral/tufted cells in the olfactory bulb of awake mouse. The trial-to-trial response jitter averaged 12 ms, a precision comparable to other sensory systems. Individual cells expressed odor-specific temporal patterns of activity and, across the population, onset times tiled the duration of the sniff cycle. Responses were more tightly time-locked to the sniff phase than to the time after inhalation onset. The spikes of single neurons carried sufficient information to discriminate odors. In addition, precise locking to sniff phase may facilitate ensemble coding by making synchrony relationships across neurons robust to variation in sniff rate. The temporal specificity of mitral/tufted cell output provides a potentially rich source of information for downstream olfactory areas.
PMID: 21765422 [PubMed - indexed for MEDLINE]
Vesicular glutamate transport at a central synapse limits the acuity of visual perception in zebrafish.
Neuron. 2007 Jan 04;53(1):65-77
Authors: Smear MC, Tao HW, Staub W, Orger MB, Gosse NJ, Liu Y, Takahashi K, Poo MM, Baier H
Abstract
The neural circuitry that constrains visual acuity in the CNS has not been experimentally identified. We show here that zebrafish blumenkohl (blu) mutants are impaired in resolving rapid movements and fine spatial detail. The blu gene encodes a vesicular glutamate transporter expressed by retinal ganglion cells. Mutant retinotectal synapses release less glutamate, per vesicle and per terminal, and fatigue more quickly than wild-type in response to high-frequency stimulation. In addition, mutant axons arborize more extensively, thus increasing the number of synaptic terminals and effectively normalizing the combined input to postsynaptic cells in the tectum. This presumably homeostatic response results in larger receptive fields of tectal cells and a degradation of the retinotopic map. As predicted, mutants have a selective deficit in the capture of small prey objects, a behavior dependent on the tectum. Our studies successfully link the disruption of a synaptic protein to complex changes in neural circuitry and behavior.
PMID: 17196531 [PubMed - indexed for MEDLINE]
Forward genetic analysis of visual behavior in zebrafish.
PLoS Genet. 2005 Nov;1(5):e66
Authors: Muto A, Orger MB, Wehman AM, Smear MC, Kay JN, Page-McCaw PS, Gahtan E, Xiao T, Nevin LM, Gosse NJ, Staub W, Finger-Baier K, Baier H
Abstract
The visual system converts the distribution and wavelengths of photons entering the eye into patterns of neuronal activity, which then drive motor and endocrine behavioral responses. The gene products important for visual processing by a living and behaving vertebrate animal have not been identified in an unbiased fashion. Likewise, the genes that affect development of the nervous system to shape visual function later in life are largely unknown. Here we have set out to close this gap in our understanding by using a forward genetic approach in zebrafish. Moving stimuli evoke two innate reflexes in zebrafish larvae, the optomotor and the optokinetic response, providing two rapid and quantitative tests to assess visual function in wild-type (WT) and mutant animals. These behavioral assays were used in a high-throughput screen, encompassing over half a million fish. In almost 2,000 F2 families mutagenized with ethylnitrosourea, we discovered 53 recessive mutations in 41 genes. These new mutations have generated a broad spectrum of phenotypes, which vary in specificity and severity, but can be placed into only a handful of classes. Developmental phenotypes include complete absence or abnormal morphogenesis of photoreceptors, and deficits in ganglion cell differentiation or axon targeting. Other mutations evidently leave neuronal circuits intact, but disrupt phototransduction, light adaptation, or behavior-specific responses. Almost all of the mutants are morphologically indistinguishable from WT, and many survive to adulthood. Genetic linkage mapping and initial molecular analyses show that our approach was effective in identifying genes with functions specific to the visual system. This collection of zebrafish behavioral mutants provides a novel resource for the study of normal vision and its genetic disorders.
PMID: 16311625 [PubMed - indexed for MEDLINE]
Regulation of axon growth in vivo by activity-based competition.
Nature. 2005 Apr 21;434(7036):1022-6
Authors: Hua JY, Smear MC, Baier H, Smith SJ
Abstract
The formation of functional neural networks requires precise regulation of the growth and branching of the terminal arbors of axons, processes known to be influenced by early network electrical activity. Here we show that a rule of activity-based competition between neighbouring axons appears to govern the growth and branching of retinal ganglion cell (RGC) axon arbors in the developing optic tectum of zebrafish. Mosaic expression of an exogenous potassium channel or a dominant-negative SNARE protein was used to suppress electrical or neurosecretory activity in subsets of RGC axons. Imaging in vivo showed that these forms of activity suppression strongly inhibit both net growth and the formation of new branches by individually transfected RGC axon arbors. The inhibition is relieved when the activity of nearby 'competing' RGC axons is also suppressed. These results therefore identify a new form of activity-based competition rule that might be a key regulator of axon growth and branch initiation.
PMID: 15846347 [PubMed - indexed for MEDLINE]
Behavioral screening assays in zebrafish.
Methods Cell Biol. 2004;77:53-68
Authors: Orger MB, Gahtan E, Muto A, Page-McCaw P, Smear MC, Baier H
PMID: 15602905 [PubMed - indexed for MEDLINE]
Perception of Fourier and non-Fourier motion by larval zebrafish.
Nat Neurosci. 2000 Nov;3(11):1128-33
Authors: Orger MB, Smear MC, Anstis SM, Baier H
Abstract
A moving grating elicits innate optomotor behavior in zebrafish larvae; they swim in the direction of perceived motion. We took advantage of this behavior, using computer-animated displays, to determine what attributes of motion are extracted by the fish visual system. As in humans, first-order (luminance-defined or Fourier) signals dominated motion perception in fish; edges or other features had little or no effect when presented with these signals. Humans can see complex movements that lack first-order cues, an ability that is usually ascribed to higher-level processing in the visual cortex. Here we show that second-order (non-Fourier) motion displays induced optomotor behavior in zebrafish larvae, which do not have a cortex. We suggest that second-order motion is extracted early in the lower vertebrate visual pathway.
PMID: 11036270 [PubMed - indexed for MEDLINE]