Determining the true polarity and amplitude of synaptic currents underlying gamma oscillations of local field potentials.
Fluctuations in successive waves of oscillatory local field potentials (LFPs) reflect the ongoing processing of neuron populations. However, their amplitude, polarity and synaptic origin are uncertain due to the blending of electric fields produced by multiple converging inputs, and the lack of a baseline in standard AC-coupled recordings. Consequently, the estimation of underlying currents by laminar analysis yields spurious sequences of inward and outward currents. We devised a combined analytical/experimental approach that is suitable to study laminated structures. The approach was essayed on an experimental oscillatory LFP as the Schaffer-CA1 gamma input in anesthetized rats, and it was verified by parallel processing of model LFPs obtained through a realistic CA1 aggregate of compartmental units. This approach requires laminar LFP recordings and the isolation of the oscillatory input from other converging pathways, which was achieved through an independent component analysis. It also allows the spatial and temporal components of pathway-specific LFPs to be separated. While reconstructed Schaffer-specific LFPs still show spurious inward/outward current sequences, these were clearly stratified into distinct subcellular domains. These spatial bands guided the localized delivery of neurotransmitter blockers in experiments. As expected, only Glutamate but not GABA blockers abolished Schaffer LFPs when applied to the active but not passive subcellular domains of pyramidal cells. The known chemical nature of the oscillatory LFP allowed an empirical offset of the temporal component of Schaffer LFPs, such that following reconstruction they yield only sinks or sources at the appropriate sites. In terms of number and polarity, some waves increased and others decreased proportional to the concomitant inputs in native multisynaptic LFPs. Interestingly, the processing also retrieved the initiation time for each wave, which can be used to discriminate afferent from postsynaptic cells in standard spike-phase correlations. The applicability of this approach to other pathways and structures is discussed.
Department of Systems Neuroscience, Cajal Institute - Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Gonzalo
G
Martín-Vázquez
Julia
J
Makarova
Valeri A
VA
Makarov
Oscar
O
Herreras
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D003198:Computer Simulation; D005260:Female; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*