Changes in Neuronal Oscillations Accompany the Loss of Hippocampal LTP that Occurs in an Animal Model of Psychosis

Abstract

The first-episode of psychosis is followed by a transient time-window of ca. 60 days during which therapeutic interventions have a higher likelihood of being effective than interventions that are started with a greater latency. This suggests that, in the immediate time-period after first-episode psychosis, functional changes occur in the brain that render it increasingly resistant to intervention. The precise mechanistic nature of these changes is unclear, but at the cognitive level, sensory and hippocampus-based dysfunctions become increasingly manifest. In an animal model of first-episode psychosis that comprises acute treatment of rats with the irreversible N-methyl-D-aspartate receptor (NMDAR)-antagonist, MK801, acute but also chronic deficits in long-term potentiation (LTP) and spatial memory occur. Neuronal oscillations, especially in the form of information transfer through θ and γ frequency oscillations are an intrinsic component of normal information processing in the hippocampus. Changes in θ-γ coupling and power are known to accompany deficits in hippocampal plasticity. Here, we examined whether changes in δ, θ, α, β and γ oscillations, or θ-γ coupling accompany the chronic loss of LTP that is observed in the MK801-animal model of psychosis. One and 4 weeks after acute systemic treatment of adult rats with MK801, a potent loss of hippocampal in vivo LTP was evident compared to vehicle-treated controls. Overall, the typical pattern of θ-γ oscillations that are characteristic for the successful induction of LTP was altered. In particular, θ-power was lower and an uncoupling of θ-γ oscillations was evident in MK801-treated rats. The alterations in network oscillations that accompany LTP deficits in this animal model may comprise a mechanism through which disturbances in sensory information processing and hippocampal function occur in psychosis. These data suggest that the hippocampus is likely to comprise a very early locus of functional change after instigation of a first-episode psychosis-like state in rodents.

Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by mutation of the psychiatric risk geneCacna1c

“…We found a deficit in the phaseamplitude coupling between theta and slow-gamma oscillations in the CA1 area of Cacna1c +/rats, manifested specifically during the exploration of a novel environment, indicating an impaired coupling between CA1 neurons and excitatory input from area CA3 (52). Alterations in theta-gamma PAC across brain regions has been recently reported in animal models of psychosis 17 (23,62) and in schizophrenic patients (63,64), and therefore may reflect a broader spectrum of network deficits in psychoses. Taken together these results show that low dosage of Cacna1c impairs both plasticity and network activation in the hippocampus in a manner likely to contribute to the observed deficits in contextual learning and latent inhibition seen in Cacna1c +/rats.…”

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

“…These results agree with the findings that inhibition and excitation are in close connection and link studies on neuronal oscillations and the mechanisms that influence E/I balance. Finally, reduction of theta and gamma activity have been correlated with decreased LTP ( Huerta and Lisman, 1993 ; Wespatat et al, 2004 ; Stephan et al, 2009 ; Kalweit et al, 2017 ). This view is consistent with our results since LTP is reduced along with the beta and gamma powers of oscillatory activity.…”

Deletion of the endogenous TrkB.T1 receptor isoform restores the number of hippocampal CA1 parvalbumin-positive neurons and rescues long-term potentiation in pre-symptomatic mSOD1(G93A) ALS mice

“…a 20% loss of these neurons and alters hippocampal gamma (30 to 90 Hz range) oscillations (Buzsáki and Wang, 2012;Zheng et al, 2011), advocating for a pivotal role of TrkB in PVi survival and function andmore specifically -in network communication. Changes in hippocampal oscillations has been associated to changes of LTP (Bikbaev, 2007;Kalweit et al, 2017).…”