Development of network oscillations through adolescence in male and female rats.

The primary aim of this research was to study the developmental trajectory of oscillatory synchronization in neural networks of normal healthy rats during adolescence, corresponding to the vulnerable age of schizophrenia prodrome in human. To monitor the development of oscillatory networks through adolescence we used a "pseudo-longitudinal" design. Recordings were performed in terminal experiments under urethane anesthesia, every day from PN32 to PN52 using rats-siblings from the same mother, to reduce individual innate differences between subjects.

Differential Effect of Dopamine D4 Receptor Activation on Low-Frequency Oscillations in the Prefrontal Cortex and Hippocampus May Bias the Bidirectional Prefrontal-Hippocampal Coupling.

Dopamine D4 receptor (D4R) mechanisms are implicated in psychiatric diseases characterized by cognitive deficits, including schizophrenia, ADHD, and autism. The cellular mechanisms are poorly understood, but impaired neuronal synchronization in cortical networks was proposed to contribute to these deficits. In animal experiments, D4R activation was shown to generate aberrant increased gamma oscillations and to reduce performance on cognitive tasks requiring functional prefrontal cortex (PFC) and hippocampus (HPC) networks.

The effect of ketamine on delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb.

Respiratory rhythm plays an important role in cognitive functions in rodents, as well as in humans. Respiratory related oscillation (RRO), generated in the olfactory bulb (OB), is an extrinsic rhythm imposed on brain networks. In rats, RRO can couple with intrinsic brain oscillations at theta frequency during sniffing and in the delta range outside of such episodes.

Rhythmic firing of neurons in the medulla of conscious freely behaving rats: rhythmic coupling with baroreceptor input.

Recent investigations emphasized the importance of neural control of cardiovascular adjustments in complex behaviors, including stress, exercise, arousal, sleep-wake states, and different tasks. Baroreceptor feedback is an essential component of this system acting on different time scales from maintaining stable levels of cardiovascular parameters on the long-term to rapid alterations according to behavior. The baroreceptor input is essentially rhythmic, reflecting periodic fluctuations in arterial blood pressure.

Respiratory coupling between prefrontal cortex and hippocampus of rats anaesthetized with urethane in theta and non-theta states.

Respiratory modulation of forebrain activity, long considered hard to reliably separate from breathing artefacts, has been firmly established in recent years using a variety of advanced techniques. Respiratory-related oscillation (RRO) is derived from rhythmic nasal airflow in the olfactory bulb (OB) and is conveyed to higher order brain networks, including the prefrontal cortex (PFC) and hippocampus (HC), where it may potentially contribute to communication between these structures by synchronizing their activities at the respiratory rate. RRO was shown to change with sleep-wake states; it is strongest in quiet waking, somewhat less in active waking, characterized with theta activity in the HC, and absent in sleep.

Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats.

Respiratory rhythm (RR) during sniffing is known to couple with hippocampal theta rhythm. However, outside of the short sniffing bouts, a more stable ~ 2 Hz RR was recently shown to rhythmically modulate non-olfactory cognitive processes, as well. The underlying RR coupling with wide-spread forebrain activity was confirmed using advanced techniques, creating solid premise for investigating how higher networks use this mechanism in their communication.

Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats.

An explosion of recent findings firmly demonstrated that brain activity and cognitive function in rodents and humans are modulated synchronously with nasal respiration. Rhythmic respiratory (RR) coupling of wide-spread forebrain activity was confirmed using advanced techniques, including current source density analysis, single unit firing, and phase modulation of local gamma activity, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) allowing dynamic PFC-HC coupling utilizing this input.

Effect of a 5-HT7 Receptor Antagonist on Reversal Learning in the Rat Attentional Set-Shifting Test.

5-HT7 receptor antagonism has been shown to ameliorate ketamine-induced schizophrenia-like deficits in extradimensional set-shifting using the attentional set-shifting task (ASST). However, this rodent paradigm distinguishes between several types of cognitive rigidity associated with neuropsychiatric conditions. The goal of this study was to test 5-HT7 receptor involvement in the reversal learning component of the ASST because this ability depends primarily on the orbito-frontal cortex, which shows strong 5-HT7 receptor expression.

Inferring the direction of rhythmic neural transmission via inter-regional phase-amplitude coupling (ir-PAC).

Phase-amplitude coupling (PAC) estimates the statistical dependence between the phase of a low-frequency component and the amplitude of a high-frequency component of local field potentials (LFP). To date PAC has been mainly applied to one signal. In this work, we introduce a new application of PAC to two LFPs and suggest that it can be used to infer the direction and strength of rhythmic neural transmission between distinct brain networks.

Subunit-specific NMDAR antagonism dissociates schizophrenia subtype-relevant oscillopathies associated with frontal hypofunction and hippocampal hyperfunction.

NMDAR antagonism alters mesolimbic, hippocampal, and cortical function, acutely reproducing the positive, cognitive, and negative symptoms of schizophrenia. These physiological and behavioral effects may depend differentially on NMDAR subtype- and region-specific effects. The dramatic electrophysiological signatures of NMDAR blockade in rodents include potentiated high frequency oscillations (HFOs, ∼140 Hz), likely generated in mesolimbic structures, and increased HFO phase-amplitude coupling (PAC), a phenomenon related to goal-directed behavior and dopaminergic tone.

Reciprocal Interactions between Medial Septum and Hippocampus in Theta Generation: Granger Causality Decomposition of Mixed Spike-Field Recordings.

The medial septum (MS) plays an essential role in rhythmogenesis in the hippocampus (HIPP); theta-rhythmic bursts of MS neurons are believed to drive theta oscillations in rats' HIPP. The MS theta pacemaker hypothesis has solid foundation but the MS-hippocampal interactions during different behavioral states are poorly understood. The MS and the HIPP have reciprocal connections and it is not clear in particular what role, if any, the strong HIPP to MS projection plays in theta generation.

Impaired reversal learning in an animal model of anorexia nervosa.

Background: Clinical investigations indicate that anorexia nervosa (AN) is associated with impaired cognitive flexibility. Activity-based anorexia (ABA), a rodent behavioral model of AN, is characterized by compulsive wheel running associated with voluntary food restriction and progressive weight loss. The goal of this study was to test whether ABA is associated with impaired cognitive flexibility.

Prefrontal-hippocampal coupling by theta rhythm and by 2-5 Hz oscillation in the delta band: The role of the nucleus reuniens of the thalamus.

Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4-8 Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists.

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases.

Assessing Granger Causality in Electrophysiological Data: Removing the Adverse Effects of Common Signals via Bipolar Derivations.

Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent.

Brain rhythms connect impaired inhibition to altered cognition in schizophrenia.

In recent years, schizophrenia research has focused on inhibitory interneuron dysfunction at the level of neurobiology and on cognitive impairments at the psychological level. Reviewing both experimental and computational findings, we show how the temporal structure of the activity of neuronal populations, exemplified by brain rhythms, can begin to bridge these levels of complexity. Oscillations in neuronal activity tie the pathophysiology of schizophrenia to alterations in local processing and large-scale coordination, and these alterations in turn can lead to the cognitive and perceptual disturbances observed in schizophrenia.

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations.

Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness.

Enhancement of gamma activity after selective activation of dopamine D4 receptors in freely moving rats and in a neurodevelopmental model of schizophrenia.

Dopamine D4 receptor (D4R) mechanisms have been implicated in several psychiatric diseases, including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and autism, which are characterized by cognitive deficits. The cellular mechanisms are poorly understood but impaired neuronal synchronization within cortical networks in the gamma frequency band has been proposed to contribute to these deficits. A D4R polymorphism was recently linked to variations in gamma power in both normal and ADHD subjects, and D4R activation was shown to enhance kainate-induced gamma oscillations in brain slices in vitro.

Impact of ketamine on neuronal network dynamics: translational modeling of schizophrenia-relevant deficits.

Subanesthetic doses of the psychomimetic, ketamine, have been used for many years to elicit behavioral effects reminiscent of schizophrenia in both healthy humans and in animal models of the disease. More recently, there has been a move toward the use of simple neurophysiological measures (event-related potentials, brain oscillations) to assay the functional integrity of neuronal circuits in schizophrenia as these measures can be assessed in patients, healthy controls, intact animals, and even in brain slices. Furthermore, alterations of these measures are correlated with basic information processing deficits that are now considered central to the disease.

Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation.

The modulatory role of 5-HT neurons and a number of different 5-HT receptor subtypes has been well documented in the regulation of sleep-wake cycles and hippocampal activity. A high level of 5-HT(6) receptor expression is present in the rat hippocampus. Further, hippocampal function has been shown to be modulated by both 5-HT(6) agonists and antagonists.