Circuits & Behavior. Daniel Huber
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1 Circuits & Behavior Daniel Huber
2 How to study circuits? Anatomy (boundaries, tracers, viral tools) Inactivations (lesions, optogenetic, pharma, accidents) Activations (electrodes, magnets, optogenetic) Recordings (electrodes, optically, fmri)
3 Model systems to study the brain:
4 Motor cortex circuits 1. Motor system Overview motor circuits Building blocks/definitions/species 2. Voluntary movements and motor cortex History Motor cortex anatomy (layers, cell types) Descending pathways 3. Functional organization of motor cortex and related areas Functional representation (microstimulation) Coding (neuronal recordings) Premotor areas 4. Brain-Machine-Interface
5 Motor circuits in mammals Brown, Sherrington, Grillner, Edgerton and others
6 Discovery of cortical motor areas Early microstimulation and lesion experiments Neck Dog Macaque Foreleg Hindleg Face Fritsch and Hitzig (1870!) Ferrier (1876) (Birth of British Anti-Vivisection Movement)
7 Discovery of cortical motor areas Oversimplified representation of early lesion and microstimulation experiments Oversimplified after Clinton Woolsey (1950) Oversimplified after Wilder Penfield (1937)
8 Discovery of cortical motor areas Oversimplified representation of early lesion and microstimulation experiments Penfield s intraoperative notes (in Schieber, 2001)
9 Primate primary motor cortex (M1) M1 M1 Central Sulcus Central Sulcus
10 3 main inputs to motor cortex 1. Cortical excitatory inputs premotor/prefrontal parietal (sensory) ipsilateral and contralateral (callosal) 2. Thalamic excitatory inputs relay nuclei: VL/VA/VM cerebello-thalamo-cortical striato-thalamo-cortical higher-order: POm Intralaminar nuclei 3. Neuromodulatory inputs noradrenergic: locus coeruleus cholinergic: basal forebrain serotonergic: dorsal raphe dopaminergic: ventral tegmental area (VTA)
11 Motor related loops Cortex Basal Ganglia/Striatum Spinal cord Subthalamic n. Zona incerta Red n. Pontine nn. Reticular n. Thalamus layer 2/3 5A 5B 6 Tree shrew M1 (Remple et al., 2006)
12 Motor related loops motor output M1 circuits sensory input Spinal systems Pons Striatum/Basal Ganglia Cerebellum Thalamus Sensory cortex Neuromodulatory systems
13 Descending motor pathways Pyramidal / Extrapyramidal Lateral / Ventrol-medial Predictive and fine control Reflexive control
14 Cortico-spinal circuits cat squirrel monkey macaque human CST CST CST CST Red Nucleus I I I I E E E E Proprio-spinal MN MN MN MN Adapted from Nakajima et al. (2000)
15 Cortico-spinal circuits cat squirrel monkey macaque human CST CST CST CST Red Nucleus I I I I E E E E Proprio-spinal MN MN MN MN Adapted from Nakajima et al. (2000)
16 Cortical mapping Early days Fritsch & Hitzig Ferrier Jackson Penfield Sherrington Nowadays Asanuma Graziano Penfield s intraoperative notes (in Schieber, 2001)
17 Cortex-muscle mapping Multiple, distributed cortical sites control any one muscle Maps of EMG responses to ICMS in M1 The same cortical sites can control different muscles Cortical colonies are organized as an overlapping mosaic UMN in cortex LMN in spinal cord muscles Andersen et al. (1975)
18 Core/surround organization CM cells labeled by rabies ICMS evoked movements Rathelot & Strick (2009)
19 Core/surround organization CM cells labeled by rabies ICMS evoked movements Rathelot & Strick (2009)
20 Longer microstimulation 0.2 ms 50 ma 200 Hz 0.5 to 1.0 sec Graziano (2007)
21 Evoking complex actions
22 What does motor cortex code? Muscle force, direction, velocity? Stimulation methods not enough; correlational methods Behavior, plus: single unit recording direction tuning spike triggered averaging (STA) stimulus triggered averaging
23 Correlation analysis Phasic-tonic cell From Evarts (1968) Tonic cell Cell s firing rates correlated with the direction and amplitude of muscle force Firing patterns very different from LMNs
24 Task specificity in M1 CM neuron EMG of muscle Precision grip Power grip
25 Firing and direction single neuron population coding Georgopoulos and colleagues
26 Practice related plasticity Motor cortex reorganization after practice, mental rehearsal, etc. shorter reaction time higher precision Reaction time (ms) Trial
27 Training and M1 activity Pascual-Leone, Hallett, et al. (1995) TMS-mapping
28 Motor equivalence The output of a planned action can be achieved with different muscles
29 Premotor areas
30 Premotor areas Romo et al. 2004
31 Brain-machine interfaces Exploiting frontal-parietal cortex signals to overcome downstream deficits Review: Nicolelis 2003
32 Brain-machine interfaces Operant conditioning of single neurons: extremely rapid plasticity process Fetz 1969 (!)
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