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Abstract

Cortical evoked response can markedly vary across presentation of identical sensory stimuli. Spontaneous
subthreshold fluctuations of the membrane potential of cortical neurons are thought to underline this variability.
During sleep or under anesthesia the activity of cortical neurons is highly synchronized. Their membrane potential
fluctuates between de- and hyperpolarized levels, also known as UP/DOWN states. Previous studies have shown
that such intracellular states can be predicted by the local field potential (LFP) and multi unity activity (MUA).
This study examined the effect of LC electrical microstimulation on whisker-evoked responses in barrel cortex
of urethane anesthetized rats by analyzing sensory response during predicted UP or DOWN states. LFP signal
was recorded from 32-channel microelectrode array with 50 microns interchannel distance and Current Source-
Density (CSD) profiles were derived. After deflection on and offset of principle whisker (2 mm, 200 ms) current
sinks we generated in layer IV of the corresponding barrel field, reflecting thalamic input. The dynamic of current
flow markedly differed between UP and DOWN states. Deflection onset produced high amplitude (0.19 ± 0.1 mV/
mm2) and long lasting current sink during DOWN state, while during UP state current sink was significant smaller
(0.07 + 0.2 mV/mm2) and followed by a long lasting reversion of polarity (100-120 ms). LC stimulation resulted in a
systematic shift of cortical LFPs from a synchronized to a desynchronized state. We used trains of biphasic square
pulses 0.5 ms, 100 mA, 5 pulses at 100 Hz. The desynchronization was transient and relatively short-lasting. 3 trains
(250 ms inter-train interval) produced ~1 sec desynchronization. CSD analysis showed that the cortical response
profile followed by a priming LC stimulation was similar to such during UP state. Our results demonstrate that LC
electrical stimulation alters the dynamics of cortical network as reflected in LFP signal. Moreover, LC discharge
and accompanying noradrenaline (NE) release from the terminal fields of LC-NE neurons may shift the membrane
potential of somatosensory neurons toward threshold level. This is consistent with previous observations that
LC activation facilitates phasic response of sensory neurons in primary somatosensory cortex. We conclude that
the smaller amplitude of current sink during UP state and after LC activation is result of a smaller driving force of
the network at the moment of sensory input, and it is not due reduction of synaptic input to the somatosensory
network.