Low-Dimensional and Monotonic Preparatory Activity in Mouse Anterior Lateral Motor Cortex

Neurons in multiple brain regions fire trains of action potentials anticipating specific movements, but this “preparatory activity” has not been systematically compared across behavioral tasks. We compared preparatory activity in auditory and tactile delayed-response tasks in male mice. Skilled, directional licking was the motor output. The anterior lateral motor cortex (ALM) is necessary for motor planning in both tasks. Multiple features of ALM preparatory activity during the delay epoch were similar across tasks. First, most neurons showed direction-selective activity and spatially intermingled neurons were selective for either movement direction. Second, many cells showed mixed coding of sensory stimulus and licking direction, with a bias toward licking direction. Third, delay activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar direction selectivity showed high spike-count correlations. Our study forms the foundation to analyze the neural circuit mechanisms underlying preparatory activity in a genetically tractable model organism. SIGNIFICANCE STATEMENT Short-term memories link events separated in time. Neurons in the frontal cortex fire trains of action potentials anticipating specific movements, often seconds before the movement. This “preparatory activity” has been observed in multiple brain regions, but has rarely been compared systematically across behavioral tasks in the same brain region. To identify common features of preparatory activity, we developed and compared preparatory activity in auditory and tactile delayed-response tasks in mice. The same cortical area is necessary for both tasks. Multiple features of preparatory activity, measured with high-density silicon probes, were similar across tasks. We find that preparatory activity is low-dimensional and monotonic. Our study forms a foundation for analyzing the circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

[1]  S. Arber,et al.  A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling , 2005, PLoS biology.

[2]  Nuo Li,et al.  Robust neuronal dynamics in premotor cortex during motor planning , 2016, Nature.

[3]  Zachary F Mainen,et al.  Neural antecedents of self-initiated actions in secondary motor cortex , 2014, Nature Neuroscience.

[4]  G. E. Alexander,et al.  Neuron Activity Related to Short-Term Memory , 1971, Science.

[5]  Masaki Tanaka,et al.  Cognitive Signals in the Primate Motor Thalamus Predict Saccade Timing , 2007, The Journal of Neuroscience.

[6]  P. Goldman-Rakic.  Cellular basis of working memory , 1995, Neuron.

[7]  D Kleinfeld,et al.  Sequential state generation by model neural networks. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Liberman,et al.  Response properties of single auditory nerve fibers in the mouse. , 2005, Journal of neurophysiology.

[9]  R. Reid,et al.  Broadly Tuned Response Properties of Diverse Inhibitory Neuron Subtypes in Mouse Visual Cortex , 2010, Neuron.

[10]  Y. Miyashita.  Neuronal correlate of visual associative long-term memory in the primate temporal cortex , 1988, Nature.

[11]  Matthew T. Kaufman,et al.  Cortical Preparatory Activity: Representation of Movement or First Cog in a Dynamical Machine? , 2010, Neuron.

[12]  Byron M. Yu,et al.  Neural Variability in Premotor Cortex Provides a Signature of Motor Preparation , 2006, The Journal of Neuroscience.

[13]  W. O'Neill,et al.  Age-Related Hearing Loss in C57BL/6J Mice has both Frequency-Specific and Non-Frequency-Specific Components that Produce a Hyperacusis-Like Exaggeration of the Acoustic Startle Reflex , 2007, Journal of the Association for Research in Otolaryngology.

[14]  Sergey L. Gratiy,et al.  Real-time spike sorting platform for high-density extracellular probes with ground-truth validation and drift correction , 2017, bioRxiv.

[15]  Hatim A. Zariwala,et al.  Neural correlates, computation and behavioural impact of decision confidence , 2008, Nature.

[16]  Karel Svoboda,et al.  Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice , 2010, Nature.

[17]  Sergey L. Gratiy,et al.  Fully integrated silicon probes for high-density recording of neural activity , 2017, Nature.

[18]  T. Ono,et al.  Retrospective and prospective coding for predicted reward in the sensory thalamus , 2001, Nature.

[19]  G. Buzsáki,et al.  Cell Assembly Sequences Arising from Spike Threshold Adaptation Keep Track of Time in the Hippocampus , 2011, The Journal of Neuroscience.

[20]  R. Andersen,et al.  Memory related motor planning activity in posterior parietal cortex of macaque , 1988, Experimental Brain Research.

[21]  Mark S. Goldman,et al.  Memory without Feedback in a Neural Network , 2009, Neuron.

[22]  Sandro Romani,et al.  Discrete attractor dynamics underlying selective persistent activity in frontal cortex , 2017, bioRxiv.

[23]  G. E. Alexander,et al.  Preparation for movement: neural representations of intended direction in three motor areas of the monkey. , 1990, Journal of neurophysiology.

[24]  Christos Constantinidis,et al.  Stable population coding for working memory coexists with heterogeneous neural dynamics in prefrontal cortex , 2016, Proceedings of the National Academy of Sciences.

[25]  Joaquín M. Fuster,et al.  Cortex and Memory: Emergence of a New Paradigm , 2009, Journal of Cognitive Neuroscience.

[26]  Tsai-Wen Chen,et al.  A Map of Anticipatory Activity in Mouse Motor Cortex , 2017, Neuron.

[27]  B. Segee,et al.  Methods in Neuronal Modeling: from Ions to Networks, 2nd Edition , 1999, Computing in Science & Engineering.

[28]  K. Svoboda,et al.  A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging , 2016, bioRxiv.

[29]  Stephen I. Ryu,et al.  Neural Dynamics of Reaching following Incorrect or Absent Motor Preparation , 2014, Neuron.

[30]  Wenjun Yan,et al.  Medial prefrontal activity during delay period contributes to learning of a working memory task , 2014, Science.

[31]  John J Hopfield,et al.  Neurodynamics of mental exploration , 2009, Proceedings of the National Academy of Sciences.

[32]  G. Feng,et al.  Cell type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function , 2011, Nature Methods.

[33]  Surya Ganguli,et al.  On simplicity and complexity in the brave new world of large-scale neuroscience , 2015, Current Opinion in Neurobiology.

[34]  K. Svoboda,et al.  A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging , 2016, bioRxiv.

[35]  Kanter,et al.  Temporal association in asymmetric neural networks. , 1986, Physical review letters.

[36]  K. Svoboda,et al.  Neural mechanisms of movement planning: motor cortex and beyond , 2018, Current Opinion in Neurobiology.

[37]  Jonathan W. Pillow,et al.  Single-trial spike trains in parietal cortex reveal discrete steps during decision-making , 2015, Science.

[38]  Allan R. Jones,et al.  A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing , 2012, Nature Neuroscience.

[39]  J. Gold,et al.  Caudate Encodes Multiple Computations for Perceptual Decisions , 2010, The Journal of Neuroscience.

[40]  Y. Nakagawa,et al.  Sonic Hedgehog Signaling Controls Thalamic Progenitor Identity and Nuclei Specification in Mice , 2009, The Journal of Neuroscience.

[41]  Paul Miller,et al.  Dynamical systems, attractors, and neural circuits , 2016, F1000Research.

[42]  Christopher D. Harvey,et al.  Choice-specific sequences in parietal cortex during a virtual-navigation decision task , 2012, Nature.

[43]  Zengcai V. Guo,et al.  Procedures for Behavioral Experiments in Head-Fixed Mice , 2014, PloS one.

[44]  Masaki Tanaka,et al.  Cerebellar Roles in Self-Timing for Sub- and Supra-Second Intervals , 2017, The Journal of Neuroscience.

[45]  J. Assad,et al.  A cognitive signal for the proactive timing of action in macaque LIP , 2006, Nature Neuroscience.

[46]  Matthijs Verhage,et al.  A solution to dependency: using multilevel analysis to accommodate nested data , 2014, Nature Neuroscience.

[47]  G. Shepherd.  Corticostriatal connectivity and its role in disease , 2013, Nature Reviews Neuroscience.

[48]  P. Goldman-Rakic,et al.  Correlated discharges among putative pyramidal neurons and interneurons in the primate prefrontal cortex. , 2002, Journal of neurophysiology.

[49]  Zengcai V. Guo,et al.  A motor cortex circuit for motor planning and movement , 2015, Nature.

[50]  M. Sahani,et al.  Cortical control of arm movements: a dynamical systems perspective. , 2013, Annual review of neuroscience.

[51]  G. Buzsáki,et al.  Memory, navigation and theta rhythm in the hippocampal-entorhinal system , 2013, Nature Neuroscience.

[52]  Zengcai V. Guo,et al.  Flow of Cortical Activity Underlying a Tactile Decision in Mice , 2014, Neuron.

[53]  Christopher D. Harvey,et al.  Recurrent Network Models of Sequence Generation and Memory , 2016, Neuron.

[54]  A. Riehle,et al.  Monkey primary motor and premotor cortex: single-cell activity related to prior information about direction and extent of an intended movement. , 1989, Journal of neurophysiology.

[55]  H. Niki,et al.  Prefrontal cortical unit activity and delayed alternation performance in monkeys. , 1971, Journal of neurophysiology.

[56]  Zengcai V. Guo,et al.  Maintenance of persistent activity in a frontal thalamocortical loop , 2017, Nature.

[57]  P. Goldman-Rakic,et al.  Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. , 1989, Journal of neurophysiology.

[58]  C. Koch,et al.  Methods in Neuronal Modeling: From Ions to Networks , 1998 .

[59]  J. Schall,et al.  Neural Control of Voluntary Movement Initiation , 1996, Science.

[60]  Jeffrey C. Erlich,et al.  A Cortical Substrate for Memory-Guided Orienting in the Rat , 2011, Neuron.

[61]  R. Romo,et al.  Neuronal correlates of parametric working memory in the prefrontal cortex , 1999, Nature.

[62]  Ralf D. Wimmer,et al.  Thalamic amplification of cortical connectivity sustains attentional control , 2017, Nature.

[63]  J. Tanji,et al.  Anticipatory activity of motor cortex neurons in relation to direction of an intended movement. , 1976, Journal of neurophysiology.

[64]  Byron M. Yu,et al.  Dimensionality reduction for large-scale neural recordings , 2014, Nature Neuroscience.

[65]  R. Wurtz,et al.  Activity of superior colliculus in behaving monkey. 3. Cells discharging before eye movements. , 1972, Journal of neurophysiology.

[66]  C. Bruce,et al.  Primate frontal eye fields. I. Single neurons discharging before saccades. , 1985, Journal of neurophysiology.

[67]  M. Shadlen,et al.  A representation of the hazard rate of elapsed time in macaque area LIP , 2005, Nature Neuroscience.