Local NMDA receptor hypofunction evokes generalized effects on gamma and high-frequency oscillations and behavior

Pharmaco‐electroencephalographic responses in the rat differ between active and inactive locomotor states

“…The significant alterations in oscillatory activity during locomotion show that electrophysiological effects of a pharmacological compound may be largely influenced by induced changes in the total duration of active locomotion, which can cause false interpretation of the impact of the compound on the brain. To overcome this pitfall in the evaluation of pharmacological modulation of brain signalling, locomotion has previously been controlled by placing rodents on a rotating drum (Krijzer et al., ; Visser et al., ), animals have been sedated or anaesthetized (Hakami et al., ), or behaviours have been scored manually (Coenen & van Luijtelaar, ; van Lier et al., ) or with computational methods (Lee et al., ; Niell & Stryker, ) in order to investigate the pharmacological modulation for one type of behaviour specifically. Some drawbacks of these methods are that (a) forced locomotion can be expected to impose more noise, motion‐related artefacts, and brain signalling related to locomotion in the signals, and for low speeds a constant level of locomotor activity may not be ensured, (b) sedated or anesthetized brain states may not reflect the awake state, (c) manual scoring of spontaneous behaviour is strenuous and tedious work with low time‐resolution, and (d) lack of validation of computational methods for behaviour scoring prevents assessment of the credibility of results.…”

“…Some drawbacks of these methods are that (a) forced locomotion can be expected to impose more noise, motion‐related artefacts, and brain signalling related to locomotion in the signals, and for low speeds a constant level of locomotor activity may not be ensured, (b) sedated or anesthetized brain states may not reflect the awake state, (c) manual scoring of spontaneous behaviour is strenuous and tedious work with low time‐resolution, and (d) lack of validation of computational methods for behaviour scoring prevents assessment of the credibility of results. Recently (Lee et al., ),investigated behaviour‐specific effects of NMDAR‐antagonists using a measure of “distance travelled” obtained with EthoVision to classify stationary, walking and running behaviours in long epochs of 5 min. Lee et al.…”

“…In contemporary schizophrenia research, neuronal oscillations have received much attention. Non‐competitive NMDAR antagonists increase gamma while antipsychotics reduce both gamma and locomotor activity (Ahnaou, Huysmans, van de Casteele, & Drinkenburg, ), however, findings that ketamine‐induced gamma (Hakami et al., ; Nicolás et al., ) and HFO (Hunt et al., ; Lee, Hudson, O'Brien, Nithianantharajah, & Jones, ) correlate with the level of locomotor activity have demonstrated the need to determine whether changes in ECoG/LFP simply reflect drug‐induced hyperlocomotion or not. In support for a locomotion‐independent effect on gamma oscillations, Hakami et al.…”

“…In the awake state, drug‐effects on LFP/ECoG evaluated specifically within a behavioural state have most often been obtained through manual behavioural scoring (Coenen & van Luijtelaar, ; Leccese, Marquis, Mattia, & Moreton, ; Sławińska & Kasicki, ; van Lier, Drinkenburg, van Eeten, & Coenen, ), which is tedious and time‐consuming work possibly prone to varying detection‐precision. Although technical solutions to track locomotor activity in rodents have been used for long (Schmitt & Hiemke, ), and behavioural‐state classification methods have been developed and validated against manual scoring (Belic, Halje, Richter, Petersson, & Kotaleski, ; Dollar, Rabaud, Garrison, & Belongie, ; Farah, Langlois, & Bilodeau, ; Jhuang et al., ; Steele, Jackson, King, & Lindquist, ; van Dam et al., ; Zarringhalam et al., ) we have found that studies, analysing LFP/ECoG in specific automatically detected states, use methods unvalidated against manual scoring (Ahnaou, Huysmans, Biermans, Manyakov, & Drinkenburg, ; Ahnaou, Huysmans, van de Casteele, et al., ; Kealy, Commins, & Lowry, ; Lee et al., ). How well behaviour is classified inevitably determines the reliability of subsequent state‐specific analyses, thus employing methods with high classification performance and time‐resolution is important.…”

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

“…Similarly, the application of a single MK‐801 dose to both HPC and PFC slices from rats causes a marked increase in LFP power in the gamma band . Interestingly, local application to either the PFC or the HPC results in similar changes in oscillatory activity as systemic injection . Similar alterations have been demonstrated in healthy human subjects receiving ketamine.…”