Showing papers by "Anthony M. Zador published in 2013"

Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination

Abstract: The neural pathways by which information about the acoustic world reaches the auditory cortex are well characterized, but how auditory representations are transformed into motor commands is not known. Here we use a perceptual decision-making task in rats to study this transformation. We demonstrate the role of corticostriatal projection neurons in auditory decisions by manipulating the activity of these neurons in rats performing an auditory frequency-discrimination task. Targeted channelrhodopsin-2 (ChR2)-mediated stimulation of corticostriatal neurons during the task biased decisions in the direction predicted by the frequency tuning of the stimulated neurons, whereas archaerhodopsin-3 (Arch)-mediated inactivation biased decisions in the opposite direction. Striatal projections are widespread in cortex and may provide a general mechanism for the control of motor decisions by sensory cortex.

Up states are rare in awake auditory cortex.

Abstract: The dynamics of subthreshold membrane potential provide insight into the organization of activity in neural circuits. In many brain areas, membrane potential is bistable, transiting between a relatively hyperpolarized down state and a depolarized up state. These up and down states, which have been proposed to play a number of computational roles, have mainly been studied in anesthetized and in vitro preparations. Here, we have used intracellular recordings to characterize the dynamics of membrane potential in the auditory cortex of awake rats. We find that long up states are rare in the awake auditory cortex, with only 0.4% of up states >500 ms. Most neurons displayed only brief up states (bumps) and spent on average ∼1% of recording time in up states >500 ms. We suggest that the near absence of long up states in awake auditory cortex may reflect an adaptation to the rapid processing of auditory stimuli.

Conneconomics: The Economics of Large-Scale Neural Connectomics

Abstract: We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50 to 100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k to $1 million or a mouse cortical connectome for $10k to $100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.

Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics

Abstract: We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50 to 100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k to $1 million or a mouse cortical connectome for $10k to $100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.