Cohen Lawrence B.

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Cohen
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Lawrence B.
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  • Preprint
    Odorant specificity of three oscillations and the DC signal in the turtle olfactory bulb
    ( 2002-11-16) Lam, Ying-Wan ; Cohen, Lawrence B. ; Zochowski, Michal R.
    The odour-induced population response in the in vivo turtle (Terepene sp.) olfactory bulb consists of three oscillatory components (rostral, middle and caudal) that ride on top of a DC signal. In an initial step to determine the functional role of these four signals, we compared the signals elicited by different odorants. Most experiments compared isoamyl acetate and cineole, odorants which have very different maps of input to olfactory bulb glomeruli in the turtle and a different perceptual quality for humans. We found substantial differences in the response to the two odours in the rise-time of the DC signal and in the latency of the middle oscillation. The rate of rise for cineole was twice as fast as that for isoamyl acetate. Similarly, the latency for the middle oscillation was about twice as long for isoamyl acetate as it was for cineole. On the other hand, a number of characteristics of the signals were not substantially different for the two odorants. These included the latency of the rostral and caudal oscillation, the frequency and envelope of all three oscillations and their locations and spatial extents. A smaller number of experiments were carried out with hexanone and hexanal; the oscillations elicited by these odorants did not appear to be different from those elicited by isoamyl acetate and cineole. Qualitative differences between the oscillations in the turtle and those in two invertebrate phyla suggest that different odour processing strategies may be used.
  • Article
    Sparsened neuronal activity in an optogenetically activated olfactory glomerulus
    (Nature Publishing Group, 2018-10-08) Braubach, Oliver R. ; Tombaz, Tuce ; Geiller, Tristan ; Homma, Ryota ; Bozza, Thomas ; Cohen, Lawrence B. ; Choi, Yunsook
    Glomeruli are the functional units of olfactory information processing but little remains known about their individual unit function. This is due to their widespread activation by odor stimuli. We expressed channelrhodopsin-2 in a single olfactory sensory neuron type, and used laser stimulation and simultaneous in vivo calcium imaging to study the responses of a single glomerulus to optogenetic stimulation. Calcium signals in the neuropil of this glomerulus were representative of the sensory input and nearly identical if evoked by intensity-matched odor and laser stimuli. However, significantly fewer glomerular layer interneurons and olfactory bulb output neurons (mitral cells) responded to optogenetic versus odor stimuli, resulting in a small and spatially compact optogenetic glomerular unit response. Temporal features of laser stimuli were represented with high fidelity in the neuropil of the glomerulus and the mitral cells, but not in interneurons. Increases in laser stimulus intensity were encoded by larger signal amplitudes in all compartments of the glomerulus, and by the recruitment of additional interneurons and mitral cells. No spatial expansion of the glomerular unit response was observed in response to stronger input stimuli. Our data are among the first descriptions of input-output transformations in a selectively activated olfactory glomerulus.
  • Preprint
    Perceptual stability during dramatic changes in olfactory bulb activation maps and dramatic declines in activation amplitudes
    ( 2007-03-30) Homma, Ryota ; Cohen, Lawrence B. ; Kosmidis, E. K. ; Youngentob, S. L.
    We measured the concentration dependence of the ability of rats to identify odorants and compared these results with the calcium signals in the nerve terminals of the olfactory receptor neurons. Odorant identification remained far above random chance at all concentrations tested (between 0.0006% and 35% of saturated vapor). In contrast the calcium signals were much smaller than their maximum values at odorant concentrations less than 1% of saturated vapor. Extrapolation suggests that only a few spikes in olfactory sensory neurons may be sufficient for correct odorant identification.
  • Preprint
    Optical analysis of circuitry for respiratory rhythm in isolated brainstem of foetal mice
    ( 2008-09) Muller, Kenneth J. ; Tsechpenakis, Gavriil ; Homma, Ryota ; Nicholls, John G. ; Cohen, Lawrence B. ; Eugenin, Jaime
    Respiratory rhythms arise from neurons situated in the ventral medulla. We are investigating their spatial and functional relationships optically by measuring changes in intracellular calcium using the fluorescent, calcium-sensitive dye Oregon Green 488 BAPTA-1 AM while simultaneously recording the regular firing of motoneurons in the phrenic nerve in isolated brainstem/spinal cord preparations of E17 to E19 mice. Responses of identified cells are associated breath by breath with inspiratory and expiratory phases of respiration and depend on CO2 and pH levels. Optical methods including two-photon microscopy are being developed together with computational analyses. Analysis of the spatial pattern of neuronal activity associated with respiratory rhythm, including cross-correlation analysis, reveals a network distributed in the ventral medulla with intermingling of neurons that are active during separate phases of the rhythm. Our experiments, aimed at testing whether initiation of the respiratory rhythm depends on pacemaker neurons, on networks or a combination of both, suggest an important role for networks.
  • Preprint
    Representation of odorants by receptor neuron input to the mouse olfactory bulb
    ( 2001-04-13) Wachowiak, Matt ; Cohen, Lawrence B.
    To visualize odorant representations by receptor neuron input to the mouse olfactory bulb, we loaded receptor neurons with calcium-sensitive dye and imaged odorant-evoked responses from their axon terminals. Fluorescence increases reflected activation of receptor neuron populations converging onto individual glomeruli. We report several findings. First, five glomeruli were identifiable across animals based on their location and odorant responsiveness; all five showed complex response specificities. Second, maps of input were chemotopically organized at near-threshold concentrations but, at moderate concentrations, involved many widely distributed glomeruli. Third, the dynamic range of input to a glomerulus was greater than that reported for individual receptor neurons. Finally, odorant activation slopes could differ across glomeruli, and for different odorants activating the same glomerulus. These results imply a high degree of complexity in odorant representations at the level of olfactory bulb input.
  • Article
    In vivo functional properties of juxtaglomerular neurons in the mouse olfactory bulb
    (Frontiers Media S.A., 2013-02-21) Homma, Ryota ; Kovalchuk, Yuri ; Konnerth, A. ; Cohen, Lawrence B. ; Garaschuk, Olga
    Juxtaglomerular neurons represent one of the largest cellular populations in the mammalian olfactory bulb yet their role for signal processing remains unclear. We used two-photon imaging and electrophysiological recordings to clarify the in vivo properties of these cells and their functional organization in the juxtaglomerular space. Juxtaglomerular neurons coded for many perceptual characteristics of the olfactory stimulus such as (1) identity of the odorant, (2) odorant concentration, (3) odorant onset, and (4) offset. The odor-responsive neurons clustered within a narrow area surrounding the glomerulus with the same odorant specificity, with ~80% of responding cells located ≤20 μm from the glomerular border. This stereotypic spatial pattern of activated cells persisted at different odorant concentrations and was found for neurons both activated and inhibited by the odorant. Our data identify a principal glomerulus with a narrow shell of juxtaglomerular neurons as a basic odor coding unit in the glomerular layer and underline the important role of intraglomerular circuitry.
  • Article
    Monitoring brain activity with protein voltage and calcium sensors
    (Nature Publishing Group, 2015-05-13) Storace, Douglas A. ; Braubach, Oliver R. ; Jin, Lei ; Cohen, Lawrence B. ; Sung, Uhna
    Understanding the roles of different cell types in the behaviors generated by neural circuits requires protein indicators that report neural activity with high spatio-temporal resolution. Genetically encoded fluorescent protein (FP) voltage sensors, which optically report the electrical activity in distinct cell populations, are, in principle, ideal candidates. Here we demonstrate that the FP voltage sensor ArcLight reports odor-evoked electrical activity in the in vivo mammalian olfactory bulb in single trials using both wide-field and 2-photon imaging. ArcLight resolved fast odorant-responses in individual glomeruli, and distributed odorant responses across a population of glomeruli. Comparisons between ArcLight and the protein calcium sensors GCaMP3 and GCaMP6f revealed that ArcLight had faster temporal kinetics that more clearly distinguished activity elicited by individual odorant inspirations. In contrast, the signals from both GCaMPs were a saturating integral of activity that returned relatively slowly to the baseline. ArcLight enables optical electrophysiology of mammalian neuronal population activity in vivo.
  • Preprint
    Optical recording from respiratory pattern generator of fetal mouse brainstem reveals a distributed network
    ( 2005-10-17) Eugenin, Jaime ; Nicholls, John G. ; Cohen, Lawrence B. ; Muller, Kenneth J.
    Unfailing respiration depends on neural mechanisms already present in mammals before birth. Experiments were made to determine how inspiratory and expiratory neurons are grouped in the brainstem of fetal mice. A further aim was to assess whether rhythmicity arises from a single pacemaker or is generated by multiple sites in the brainstem. To measure neuronal firing, a fluorescent calcium indicator dye was applied to embryonic central nervous systems isolated from mice. While respiratory commands were monitored electrically from third to fifth cervical ventral roots, activity was measured optically over areas containing groups of respiratory neurones, or single neurones, along the medulla from the facial nucleus to the pre-Bötzinger complex. Large optical signals allowed recordings to be made during individual respiratory cycles. Inspiratory and expiratory neurones were intermingled. A novel finding was that bursts of activity arose in a discrete area intermittently, occurring during some breaths, but failing in others. Raised CO2 partial pressure or lowered pH increased the frequency of respiration; neurons then fired reliably with every cycle. Movies of activity revealed patterns of activation of inspiratory and expiratory neurones during successive respiratory cycles; there was no evidence for waves spreading systematically from region to region. Our results suggest that firing of neurons in immature respiratory circuits is a stochastic process, and that the rhythm does not depend on a single pacemaker. Respiratory circuits in fetal mouse brainstem appear to possess a high safety factor for generating rhythmicity, which may or may not persist as development proceeds.