Large Scale recording of neuronal activity in behaving rodents
Want to separate the types neurons of they record from and control.
Step 1 : extract single neurons from extracellular electrodes
Extracellular electrode arrys give best spatiotemporal resolution at depth in awake freely moving rodent.
Neurons are not point sources of action potentials. The action potential back propagates to dendrites.
Extracellular fields of many neurons strongly overlap.
Can be fooled if you look just in one layer, an action potential recorded in layer IV may actually originate in layer 5.
Try to infer intracellular features from extracellular recording properties.
Depolarization of the cell during AP chages its intracellular waveform and is refelected in the extracellular waveform. Hence wave-shape sorting algorhitms can be fooled by changing depolarization levels.
Use multidimensional clustering to figure out which spikes come from which neurons.
Step 2 : From single neurons to neuron types (taxonomy)
Compare the timing of spiking of each neuron relative to the theta cycle. Also compare in the sharp wave cycle.
After 6 years of works, they classify constellations of neurons involved in different network patterns.
Interneurons : Timers and segreators. Timing is locked to theta cycle.
Looking at the assembly patterns you can predict the choice of an animal.
In prefrontal cortex. Use cross-correlation techniques across the population that is recorded.
Short latency large narrow peak indicates monosynaptic excitatory connection. Pyramidal -> Interneurons.
Short latency spike suppression indicates monosynaptic inhibition. Inter-> Pyr
Has a database of >2500 neurons. Comparte peak latency and waveshape to the correlation data that defines each as inhibitory or excitatory. These two groups cluster in the peak latency vs. waveshape space. So now they have a signature to classify excitatory or inhibitory neurons.
Interacting with circuits
Determine the neuron types
Perturb the correlations with optogenetics to test hypotheses
Simultaneous recoding and stimulation with optical fiber attached to silicon probe (Sebastian Royer @ Janelia)
Figure 8 maze.
Can record place cells that have characteristic firing pattern during running through the maze. Can see CHr2 stimulation in some cells. Neurons fire in stereotyped pattern with theta cycle except when stimulated with ChR2, then it follows the ChR2 stimulation cycle.
Better probes, stimulating on every shank rather than just one shank.
Larger density recording sites
Further volume reduction
Identification of neurons
Light activation and scilencing of neurons
Improved neurron clustering algorithims