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University of Nottingham Medical School Neuronal Networks Laboratory

Neuronal Networks Laboratory. University of Nottingham Medical School Neuronal Networks Laboratory. Using Plexon at Nottingham: Sensory Gating, Anxiety, Seizures, and Pain Dr Rob Mason School of Biomedical Sciences University of Nottingham Medical School. Neuronal

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University of Nottingham Medical School Neuronal Networks Laboratory

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  1. Neuronal Networks Laboratory University of Nottingham Medical School Neuronal Networks Laboratory Using Plexon at Nottingham: Sensory Gating, Anxiety, Seizures, and Pain Dr Rob Mason School of Biomedical Sciences University of Nottingham Medical School

  2. Neuronal Networks Laboratory • Talk Format • Brief overview of what we have been studying using Plexon system(s) at Nottingham • Indicate on route some hardware developments • & signal processing / analysis approaches we use • schizophrenia – sensory gating • epilepsy • anxiety • pain

  3. Multiple Electrode Recordings in vivo • simultaneous multichannel spike & field potential recording • 64-channel MAP system • 32-channel MAP system – with CinePlex for behavioural studies • 64-channel Recorder system • 16-channel Recorder system • used MAP & Recorder for in vitro MEA studies with brain slices & neuronal cultures

  4. Neuronal Networks Laboratory LAB TEAM epilepsy Ben Coomber [Dr Mike O’Donoghue] Clare Roe schizophrenia Dr Jill Suckling [Prof CA Marsden] Dr Dissanayake anxiety Dr Carl Stevenson [Prof CA Marsden] pain Dr Steve Elmes [Dr V Chapman] rodent USVs Beth Tunstall [Dr S Beckett] data analysis Margarita Zachariou [Dr S Coombes / Dr M Owen] [Mathematics Dept] Dr David Halliday (University of York) Prof D Auer (fMRI / phMRI)

  5. LAB EXPERIMENTAL DIRECTIONS mPFCx interconnectivity & functional context – in vivo studies Contralateral mPFC medial Pre-Frontal Cortex - schizophrenia - drugs of abuse VTA PVt Hippocampus nucleus Accumbens Amygdala SCN circadian - affective states maternal separation - depression • sensory gating • - schizophrenia • - epilepsy USVs - affective states

  6. Neuronal Networks Laboratory • Dual site recordings • VTA - mPFC • hippocampus - mPFC • amygdala - mPFC • mPFC - mPFC • Systemic pharmacological manipulation • Local pharmacological manipulation • “injec-trode” • integrated microiontophoresis with recording array • Electrical stimulation • Independent electrode array microdrive • Anaesthetised & awake-behaving preparations

  7. Neuronal Networks Laboratory University of Nottingham Medical School Neuronal Networks Laboratory • Project #1: Schizophrenia • auditory-evoked sensory gating • effects of PCP / ketamine- model • effects of social isolation- model

  8. VTA PFC Schizophrenia - VTA/mPFCx dual-site recordings Prussian Blue reaction - locate recording site(s) - histology ventral tegmental area - VTA medial prefrontal cortex - mPFC

  9. Neurone # 1 7 VTA cells 1 8 PFC cells VTA LFP PFC LFP 1 mV 5 s Dual site recording: pre-frontal cortical / VTA recording multiple single-units & LFPs • Matlab scripts for off-line characterisation unit spike waveforms & LFPs

  10. Local application of drugs – “injec-trode” Tubing attached to Hamilton syringe Cannula tip • Explore connectivity between PFC and VTA - • e.g. local application of drug (e.g. glutamate) • to VTA to drive mPFC Electrode headstage Electrode tips Extra-VTA PFC Extra-VTA LFP PFC LFP 10s 50 nl Glutamate (100 mM)

  11. Neuronal Networks Laboratory Sensory gating in hippocampus: A model for schizophrenia ? • Sensory gating: mechanism(s) by which irrelevant sensory information is filtered – enables efficient information processing • Auditory Conditioning-Test paradigm: measures reduction in auditory-evoked response produced by Test stimulus following a Conditioning stimulus • Stimuli: 3kHz sine-wave / 10ms duration / presented 500ms apart / 80-90dB • human P50 wave = rat N40 component • Gating absent in - schizophrenic patients (& near family members) • - normal human volunteers given PCP / amphetamine • - rats given PCP / amphetamine

  12. Units LFPs 1s LFP2 averaged 128 trials - 1 Trial # - 128 mV N40 N40 s Cs Ts Hippocampal CA3 - auditory-evoked unit & LFP activity event tone Averaged LFP T/C ratio = 50%

  13. Single-unit PSTHs ‘ rasters histograms - gating rats CA3 region CA3 region dentate gyrus Spike raster PSTH Unit 1 Unit 2 Unit 3 Unit 4 LFP trial raster LFP

  14. Hippocampal CA3 auditory-evoked unit & LFP activity Effects of PCP (1mg/kg i.p.)  attenuates/abolishes sensory gating 1 Trail # 128 Basal [128 trials] T/C ratio = 32% 45mins after PCP T/C ratio = 66%

  15. Neuronal Networks Laboratory University of Nottingham Medical School Neuronal Networks Laboratory • Project #2: Epilepsy • kainate-induced epileptiform activity – TLE • functional network interactions - hippocampus  mPFC • electrical stimulation – perforant pathway • role of endocannibnoid system – CB1R pharmacology

  16. KA-induced firing (10mg kg-1, i.p.) Basal firing PFC Hipp PFC HippL HippM 2s hippocampus mPFC Kainate-induced epileptiform activity – dual recording hippocampus & mPFC

  17. mPFC Hipp mPFC HIPP mPFC Hippocampus unit 1H Ref unit unit 2H unit 3H Hippocampal-mPFC – functional connectivity Burst analysis – Synchrony index - Cross-correlation – coherence - PDC

  18. PDC Analysis – Unit populations Identify direction of activity between hippocampus and mPFC - PDC applied: technique with potential to reveal the neuronal ensemble drive direction. KA KA Note: the magnitude of the classical coherence gives no information about directional connectivity, but its phase may do so.

  19. PDC Analysis – LFPs • Representative PDC plot between LFPs recorded from 3 electrodes in both • mPFC (AD01-08) • hippocampus (AD10 to AD16 = medial to lateral electrodes). mPFC Hippocampus mPFC Hippocampus TIME FRAME # Red boxes highlight PDC between brain regions – suggesting the predominant flow is from mPFC to hippocampus Green boxes highlight that the predominant flow within hippocampus is from lateral to medial.

  20. LFPanalyser suite 2006 – custom Matlab script • Basal (pre-KA challenge) - hippocampus

  21. LFPanalyser suite 2006 • 45min post-KA - hippocampus

  22. LFPanalyser suite 2006

  23. % Power Distribution Basal LFPanalyser suite 2006 45min Post-KA

  24. Neuronal Networks Laboratory University of Nottingham Medical School Neuronal Networks Laboratory • Project #3: • Nociception & pain management • dual spinal cord / supraspinal recording • Role of endocannabinoid system in normal physiology and pain (e.g. neuropathic) states

  25. Mechanically-evoked response in somatosensory thalamus (VPM) noxious (65g) stimulation innocuous (7g) stimulation

  26. Neuronal Networks Laboratory University of Nottingham Medical School Neuronal Networks Laboratory • Project #4: Affective state • Cortico-limibic network interactions • anxiety • effects of maternal separation • pharmacologically-induced (e.g. FG-7142) anxiety • behavioural sequalae • rodent ultrasound vocalisations

  27. nucleus accumbens – mPFC Rat ultrasound vocalisations (USVs) & affective state • Role of nuc accumbens in USV-mediated Behaviours • nucleus accumbens / basolateral amygdala - mPFCx functional connectivity 50kHz ~50 kHz calls - rewarding stimuli(Types A-F) Frequency (kHz) 22kHz ~22 kHz calls - aversive stimuli (call Type G) Neuronal Networks Laboratory Time (s)

  28. unit activity - nuc accumbens USV call start time Behavioural data Local Field Potential (LFP) USV Recorder input Spectrogram of specific calls [AviSoft] Combined unit / LFP with USV / behavioural recording

  29. Multiple Electrode Recordings in vivo simultaneous multichannel spike / field potential / behavioural recording CinePlex system Video camera

  30. Recorded video Neuronal Networks Laboratory Neural data Behavioural Electrophysiology II Circular arena recording using CinePlex Movie- rat HopScotch: 8-microwire array in nuc. accumbens - 6 weeks post implant

  31. Neuronal Networks Laboratory University of Nottingham Medical School Neuronal Networks Laboratory That’s all folks Lab web site www.nottingham.ac.uk/neuronal-networks

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