Mice With Decreased Number of Interneurons Exhibit Aberrant Spontaneous and Oscillatory Activity in the Cortex

Abstract

GABAergic (γ-aminobutyric acid) neurons are inhibitory neurons and protect neural tissue from excessive excitation. Cortical GABAergic neurons play a pivotal role for the generation of synchronized cortical network oscillations. Imbalance between excitatory and inhibitory mechanisms underlies many neuropsychiatric disorders and is correlated with abnormalities in oscillatory activity, especially in the gamma frequency range (30–80 Hz). We investigated the functional changes in cortical network activity in response to developmentally reduced inhibition in the adult mouse barrel cortex (BC). We used a mouse model that displays ∼50% fewer cortical interneurons due to the loss of Rac1 protein from Nkx2.1/Cre-expressing cells [Rac1 conditional knockout (cKO) mice], to examine how this developmental loss of cortical interneurons may affect basal synaptic transmission, synaptic plasticity, spontaneous activity, and neuronal oscillations in the adult BC. The decrease in the number of interneurons increased basal synaptic transmission, as examined by recording field excitatory postsynaptic potentials (fEPSPs) from layer II networks in the Rac1 cKO mouse cortex, decreased long-term potentiation (LTP) in response to tetanic stimulation but did not alter the pair-pulse ratio (PPR). Furthermore, under spontaneous recording conditions, Rac1 cKO brain slices exhibit enhanced sensitivity and susceptibility to emergent spontaneous activity. We also find that this developmental decrease in the number of cortical interneurons results in local neuronal networks with alterations in neuronal oscillations, exhibiting decreased power in low frequencies (delta, theta, alpha) and gamma frequency range (30–80 Hz) with an extra aberrant peak in high gamma frequency range (80–150 Hz). Therefore, our data show that disruption in GABAergic inhibition alters synaptic properties and plasticity, while it additionally disrupts the cortical neuronal synchronization in the adult BC.

Effect of Neonatal Treatment With the NMDA Receptor Antagonist, MK-801, During Different Temporal Windows of Postnatal Period in Adult Prefrontal Cortical and Hippocampal Function

“…Neuronal oscillations were analyzed as reported previously (Kalemaki et al, 2018). Twenty traces of spontaneous voltage signals (32 s each trace) were used from each brain slice.…”

Lateralized Expression of Cortical Perineuronal Nets during Maternal Experience is Dependent on MECP2

“…Perineuronal nets (PNNs) are specialized extracellular matrix structures that can act as physical barriers or modulators of plasticity, restrict axon regeneration, and form molecular brakes that actively control synaptic maturation and the function of cortical parvalbumin+ (PV+) GABAergic interneurons that drive gamma oscillations (Bartos et al, 2002;Begum and Sng, 2017;Bernard and Prochiantz, 2016;Carstens et al, 2016;Deepa et al, 2002;Dityatev et al, 2007;Donato et al, 2013;Durand et al, 2012;Frischknecht et al, 2009;Gundelfinger et al, 2010;Hartig et al, 1992;Hou et al, 2017;Kalemaki et al, 2018;Kosaka and Heizmann, 1989;Krishnan et al, 2015Krishnan et al, , 2017Nakagawa et al, 1986;Orlando et al, 2012;Pizzorusso et al, 2002Pizzorusso et al, , 2006Sigal et al, 2019;Sugiyama et al, 2009;Suttkus et al, 2012;Ueno et al, 2018;Vo et al, 2013;de Winter et al, 2016;Ye and Miao, 2013). In rodents, mature PNNs in the adult cortex are thought to be stable structures, inhibitory to plasticity, and perhaps play roles in long term memory such as "engrams" (Carstens et al, 2016;Gogolla et al, 2009;Thompson et al, 2018).…”

Activation of brain‐derived neurotrophic factor signaling in the basal forebrain reverses acute sleep deprivation‐induced fear memory impairments

“…ANA‐12 is a selective TrkB receptor antagonist without altering TrkA and TrkC functions (Cazorla et al, 2011). The aCSF served as the vehicle control, which contained (in mM/l): 125 NaCl, 3.5 KCl, 26 NaHCO 3 , 1 MgCl 2 , and 10 glucose (pH = 7.4, 315 mOsm/L) (Kalemaki, Konstantoudaki, Tivodar, Sidiropoulou, & Karagogeos, 2018). The aCSF (1 µl/side) was administrated 1 hr before behavior training.…”