Analysis of an open source, closed-loop, realtime system for hippocampal sharp-wave ripple disruption

Transient neural activity pervades hippocampal electrophysiological activity. During more quiescent states, brief ≈100 ms periods comprising large ≈150–250 Hz oscillations known as sharp-wave ripples (SWR) which co-occur with ensemble bursts of spiking activity, are regularly found in local field potentials recorded from area CA1. SWRs and their concomitant neural activity are thought to be important for memory consolidation, recall, and memory-guided decision making. Temporally-selective manipulations of hippocampal neural activity upon online hippocampal SWR detection have been used as causal evidence of the importance of SWR for mnemonic process as evinced by behavioral and/or physiological changes. However, though this approach is becoming more wide spread, the performance trade-offs involved in building a SWR detection and disruption system have not been explored, limiting the design and interpretation of SWR detection experiments. We present an open source, plug-and-play, online ripple detection system with a detailed performance characterization. Our system has been constructed to interface with an open source software platform, Trodes, and two hardware acquisition platforms, Open Ephys and SpikeGadgets. We show that our in vivo results — approximately 80% detection latencies falling in between ≈20–66 ms with ≈2 ms closed-loop latencies while maintaining <10 false detections per minute — are dependent upon both algorithmic trade-offs and acquisition hardware. We discuss strategies to improve detection accuracy and potential limitations of online ripple disruptions. By characterizing this system in detail, we present a template for analyzing other closed-loop neural detection and perturbation systems. Thus, we anticipate our modular, open source, realtime system will facilitate a wide range of carefully-designed causal closed-loop neuroscience experiments.

[1]  B. Bontempi,et al.  Sites of Neocortical Reorganization Critical for Remote Spatial Memory , 2004, Science.

[2]  J. O’Neill,et al.  Reactivation of experience-dependent cell assembly patterns in the hippocampus , 2008, Nature Neuroscience.

[3]  Caleb Kemere,et al.  Rapid and Continuous Modulation of Hippocampal Network State during Exploration of New Places , 2013, PloS one.

[4]  Jozsef Csicsvari,et al.  Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere with the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus , 2016, PloS one.

[5]  M. Fanselow,et al.  Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats , 1997, Behavioural Brain Research.

[6]  B. McNaughton,et al.  Reactivation of hippocampal ensemble memories during sleep. , 1994, Science.

[7]  G. Buzsáki Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning , 2015, Hippocampus.

[8]  D. Dupret,et al.  Hippocampal Offline Reactivation Consolidates Recently Formed Cell Assembly Patterns during Sharp Wave-Ripples , 2016, Neuron.

[9]  M. Zugaro,et al.  Learning-Induced Plasticity Regulates Hippocampal Sharp Wave-Ripple Drive , 2014, The Journal of Neuroscience.

[10]  Oxana Eschenko,et al.  Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation , 2016, Learning & memory.

[11]  L. Frank,et al.  New Experiences Enhance Coordinated Neural Activity in the Hippocampus , 2008, Neuron.

[12]  György Buzsáki,et al.  Reactivations of emotional memory in the hippocampus–amygdala system during sleep , 2017, Nature Neuroscience.

[13]  G. Buzsáki,et al.  Local Generation and Propagation of Ripples along the Septotemporal Axis of the Hippocampus , 2013, The Journal of Neuroscience.

[14]  M. Wilson,et al.  Disruption of ripple‐associated hippocampal activity during rest impairs spatial learning in the rat , 2009, Hippocampus.

[15]  G. Buzsáki,et al.  Traveling Theta Waves along the Entire Septotemporal Axis of the Hippocampus , 2012, Neuron.

[16]  Robert E. Clark,et al.  Impaired Recognition Memory in Rats after Damage to the Hippocampus , 2000, The Journal of Neuroscience.

[17]  L. Frank,et al.  Rewarded Outcomes Enhance Reactivation of Experience in the Hippocampus , 2009, Neuron.

[18]  H. Eichenbaum A cortical–hippocampal system for declarative memory , 2000, Nature Reviews Neuroscience.

[19]  Mattias P. Karlsson,et al.  Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility , 2017, eLife.

[20]  L. Frank,et al.  Awake Hippocampal Sharp-Wave Ripples Support Spatial Memory , 2012, Science.

[21]  B. Bontempi,et al.  Time-dependent reorganization of brain circuitry underlying long-term memory storage , 1999, Nature.

[22]  G. Buzsáki,et al.  Selective suppression of hippocampal ripples impairs spatial memory , 2009, Nature Neuroscience.