Project Details
Description
ABSTRACT
BRAIN Initiative-funded, large-scale approaches to classify neurons based on transcriptomic, morphological and
electrical properties have unveiled dozens of unique cell classes in the mouse brain. However, whether they
represent functionally diverse populations of relevance to animal perception and behavior remains an open
question. Dissecting their individual roles requires the integration of targeted recording techniques and
optogenetic manipulation approaches, which operate at the physiologically relevant spatiotemporal scales (i.e.
cellular resolution and millisecond timescales).
Here, we propose to use high-speed (0.4-1 kHz), genetically encoded fluorescence voltage imaging to
understand the role of distinct interneuronal populations in attentional modulation of visual processing during
visually guided behavior. First, we will establish the optical instrumentation for high-speed, dual channel voltage
imaging with non-overlapping structured illumination. We will further validate the use of our second-generation,
fluorescence resonance energy transfer (FRET)-opsin indicators Ace-mNeon2 and VARNAM2 and their reverse
response polarity variants pAce and pAceR, for concurrent voltage recordings from pairs of interneuronal
ensembles and pyramidal neurons in awake, running mice. Thereafter, using simultaneous triple-population
voltage imaging, we will assess the effects of attention on the firing rates of the three cell classes during visually
guided behavior and compute the spatiotemporal correlations in the activation patterns of neighboring neurons.
Separately, we will measure the visual tuning properties of the same neurons during presentations of drifting
grating stimuli. We will further draw a correlation between neuronal attention modulation index and feature
selectivity to test the applicability of the feature similarity gain model. Lastly, to establish causal roles in the
attentional modulation of visual responses, we will optogenetically manipulate the activity of select interneurons
in a spatially precise manner, while recording the voltage responses in neighboring pyramidal cells when mice
are engaged in the behavioral task.
Our proposed work will (1) elucidate the role of distinct interneuron-types in visual attention and enable
functional cross-comparisons within the same animals and at increased spatiotemporal resolution; (2) uncover
synergistic and antagonistic relationships between neighboring pyramidal neuron-interneuron pairs for neurons
that are positively versus negatively modulated by attention; (3) test the applicability of the feature similarity gain
model in rodents and (4) establish causal roles for distinct interneuronal populations in attentional modulation of
visual processing.
Together, our work will establish simultaneous, multipopulation voltage imaging as the preferred modality
to unravel the real-time functional differences between neuron-types in perception and behavior.
Status | Active |
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Effective start/end date | 6/1/23 → 5/31/24 |
Funding
- National Institute of Neurological Disorders and Stroke: $325,857.00
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