TY - JOUR
T1 - Isolation of the murine Glut1 deficient thalamocortical circuit
T2 - wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations
AU - Solis, Elysandra M.
AU - Good, Levi B.
AU - Vázquez, Rafael Granja
AU - Patnaik, Sourav
AU - Hernandez-Reynoso, Ana G.
AU - Ma, Qian
AU - Angulo, Gustavo
AU - Dobariya, Aksharkumar
AU - Cogan, Stuart F.
AU - Pancrazio, Joseph J.
AU - Pascual, Juan M.
AU - Jakkamsetti, Vikram
N1 - Publisher Copyright:
Copyright © 2023 Solis, Good, Vázquez, Patnaik, Hernandez-Reynoso, Ma, Angulo, Dobariya, Cogan, Pancrazio, Pascual and Jakkamsetti.
PY - 2023
Y1 - 2023
N2 - Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30–50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.
AB - Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30–50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.
KW - Glut1
KW - glucose transporter
KW - metabolism
KW - multielectrode array
KW - oscillations
KW - thalamus
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U2 - 10.3389/fnins.2023.1191492
DO - 10.3389/fnins.2023.1191492
M3 - Article
C2 - 37829723
AN - SCOPUS:85173677009
SN - 1662-4548
VL - 17
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 1191492
ER -