Chronic Electrophysiological Recordings Research Articles

Improving naturalistic neuroscience with patient engagement strategies.

The clinical implementation of chronic electrophysiology-driven adaptive deep brain stimulation (DBS) algorithms in movement disorders requires reliable representation of motor and non-motor symptoms in electrophysiological biomarkers, throughout normal life (naturalistic). To achieve this, there is the need for high-resolution and -quality chronic objective and subjective symptom monitoring in parallel to biomarker recordings. To realize these recordings, an active participation and engagement of the investigated patients is necessary. To date, there has been little research into patient engagement strategies for DBS patients or chronic electrophysiological recordings. We here present our concept and the first results of a patient engagement strategy for a chronic DBS study. After discussing the current state of literature, we present objectives, methodology and consequences of the patient engagement regarding study design, data acquisition, and study infrastructure. Nine patients with Parkinson's disease and their caregivers participated in the meeting, and their input led to changes to our study design. Especially, the patient input helped us designing study-set-up meetings and support structures. We believe that patient engagement increases compliance and study motivation through scientific empowerment of patients. While considering patient opinion on sensors or questionnaire questions may lead to more precise and reliable data acquisition, there was also a high demand for study support and engagement structures. Hence, we recommend the implementation of patient engagement in planning of chronic studies with complex designs, long recording durations or high demand for individual active study participation.

3D Printed Skull Cap and Benchtop Fabricated Microwire-Based Microelectrode Array for Custom Rat Brain Recordings.

Microwire microelectrode arrays (MEAs) have been a popular low-cost tool for chronic electrophysiological recordings and are an inexpensive means to record the electrical dynamics crucial to brain function. However, both the fabrication and implantation procedures for multi-MEAs on a single rodent are time-consuming and the accuracy and quality are highly manual skill-dependent. To address the fabrication and implantation challenges for microwire MEAs, (1) a computer-aided designed and 3D printed skull cap for the pre-determined implantation locations of each MEA and (2) a benchtop fabrication approach for low-cost custom microwire MEAs were developed. A proof-of-concept design of a 32-channel 4-MEA (8-wire each) recording system was prototyped and tested through Sprague Dawley rat recordings. The skull cap design, based on the CT-scan of a single rat conforms well with multiple Sprague Dawley rats of various sizes, ages, and weight with a minimal bregma alignment error (A/P axis standard error of the mean = 0.25 mm, M/L axis standard error of the mean = 0.07 mm, n = 6). The prototyped 32-channel system was able to record the spiking activities over five months. The developed benchtop fabrication method and the 3D printed skull cap implantation platform would enable neuroscience groups to conduct in-house design, fabrication, and implantation of customizable microwire MEAs at a lower cost than the current commercial options and experience a shorter lead time for the design modifications and iterations.

Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow-wave activity. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

Flexible High-Resolution Force and Dimpling Measurement System for Pia and Dura Penetration During In Vivo Microelectrode Insertion Into Rat Brain.

Objective:Understanding the in vivo force and tissue dimpling during micro-electrode implantation into the brain are important for neuro-electrophysiology to minimize damage while enabling accurate placement and stable chronic extracellular electrophysiological recordings. Prior studies were unable to measure the sub-mN forces exerted during in vivo insertion of small electrodes. Here, we have investigated the in vivo force and dimpling depth profiles during brain surface membrane rupture (including dura) in anesthetized rats.Methods:A µN-resolution cantilever beam-based measurement system was designed, built, and calibrated and adapted for in vivo use. A total of 244 in vivo insertion tests were conducted on 8 anesthetized rats with 121 through pia mater and 123 through dura and pia combined.Results:Both microwire tip sharpening and diameter reduction reduced membrane rupture force (insertion force) and eased brain surface penetration. But dimpling depth and rupture force are not always strongly correlated. Multi-shank silicon probes showed smaller dimpling and rupture force per shank than single shank devices.Conclusion:A force measurement system with flexible range and µN-level resolution (up to 0.032 µN) was achieved and proved feasible. For both pia-only and dura-pia penetrations in anesthetized rats, the rupture force and membrane dimpling depth at rupture are linearly related to the microwire diameter.Significance:We have developed a new system with both µN-level resolution and capacity to be used in vivo for measurement of force profiles of various neural interfaces into the brain. This allows quantification of brain tissue cutting and provides design guidelines for optimal neural interfaces.

Coordinated increase of reliable cortical and striatal ensemble activations during recovery after stroke.

SUMMARYSkilled movements rely on a coordinated cortical and subcortical network, but how this network supports motor recovery after stroke is unknown. Previous studies focused on the perilesional cortex (PLC), but precisely how connected subcortical areas reorganize and coordinate with PLC is unclear. The dorsolateral striatum (DLS) is of interest because it receives monosynaptic inputs from motor cortex and is important for learning and generation of fast reliable actions. Using a rat focal stroke model, we perform chronic electrophysiological recordings in motor PLC and DLS during long-term recovery of a dexterous skill. We find that recovery is associated with the simultaneous emergence of reliable movement-related single-trial ensemble spiking in both structures along with increased cross-area alignment of spiking. Our study highlights the importance of consistent neural activity patterns across brain structures during recovery and suggests that modulation of cross-area coordination can be a therapeutic target for enhancing motor function post-stroke.

The development of an implantable deep brain stimulation device with simultaneous chronic electrophysiological recording and stimulation in humans

Deep brain stimulation (DBS) is used to treat a wide array of neurologic conditions. However, traditional programming of stimulation parameters relies upon short term subjective observation of patient symptoms and undesired stimulation effects while in the clinic. To gain a more objective measure of the neuronal activity that contributes to patient symptoms and response to treatment, there is a clear need for a fully-implantable DBS system capable of chronically recording patient-specific electrophysiological biomarker signals over time. By providing an objective correlate of a patient's disease and response to treatment, this capability has the potential to improve therapeutic benefit while preventing undesirable side effects. Herein, the engineering and capabilities of the Percept PC, the first FDA-approved, fully-implantable DBS device capable of nearly-simultaneous electrophysiological recordings and stimulation, are discussed. The device's ability to chronically record local field potentials (LFPs) at implanted DBS leads was validated in patients with neurological disorders. Lastly, the electrophysiological activity correlates of clinically relevant patient-reported events are presented. While FDA approved for conditions such as Parkinson's disease, essential tremor, dystonia, obsessive-compulsive disorder, and epilepsy, chronic electrophysiological recordings in humans has broad applications within basic science and clinical practice beyond DBS, offering a wealth of information related to normal and abnormal neurophysiology within distinct brain areas.

Sensory Island Task (SIT): A New Behavioral Paradigm to Study Sensory Perception and Neural Processing in Freely Moving Animals.

A central function of sensory systems is the gathering of information about dynamic interactions with the environment during self-motion. To determine whether modulation of a sensory cue was externally caused or a result of self-motion is fundamental to perceptual invariance and requires the continuous update of sensory processing about recent movements. This process is highly context-dependent and crucial for perceptual performances such as decision-making and sensory object formation. Yet despite its fundamental ecological role, voluntary self-motion is rarely incorporated in perceptual or neurophysiological investigations of sensory processing in animals. Here, we present the Sensory Island Task (SIT), a new freely moving search paradigm to study sensory processing and perception. In SIT, animals explore an open-field arena to find a sensory target relying solely on changes in the presented stimulus, which is controlled by closed-loop position tracking in real-time. Within a few sessions, animals are trained via positive reinforcement to search for a particular area in the arena (“target island”), which triggers the presentation of the target stimulus. The location of the target island is randomized across trials, making the modulated stimulus feature the only informative cue for task completion. Animals report detection of the target stimulus by remaining within the island for a defined time (“sit-time”). Multiple “non-target” islands can be incorporated to test psychometric discrimination and identification performance. We exemplify the suitability of SIT for rodents (Mongolian gerbil, Meriones unguiculatus) and small primates (mouse lemur, Microcebus murinus) and for studying various sensory perceptual performances (auditory frequency discrimination, sound source localization, visual orientation discrimination). Furthermore, we show that pairing SIT with chronic electrophysiological recordings allows revealing neuronal signatures of sensory processing under ecologically relevant conditions during goal-oriented behavior. In conclusion, SIT represents a flexible and easily implementable behavioral paradigm for mammals that combines self-motion and natural exploratory behavior to study sensory sensitivity and decision-making and their underlying neuronal processing.

Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings

ObjectivesDescribe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA). MethodsClinical seizures from eight patients (mean follow-up of 10.1 years) were analyzed pre- and post-treatment. Chronic ambulatory electrocorticograms (ECoGs) recorded from PVNHs, hippocampus and neocortex were evaluated to identify the earliest electrographic seizure onset type, pattern of spread, and interictal characteristics. ResultsMean reduction in disabling seizures was 85.7 % (n = 8); seven patients had >50% seizure reduction and two were seizure-free in the final year of analysis. Seizure rate showed a progressive reduction over the course of the study with the highest rate of improvement in the first two to three years after implantation. Four of seven patients with one PVNH lead and a second lead in the hippocampus or neocortex had some electrographic seizures first recorded at either lead location, suggesting two foci or seizure propagation patterns. Low voltage fast type activity was the prominent seizure onset pattern. Interictal ECoG power was lower in PVNH than hippocampus. ConclusionsRNS® System treatment substantially reduced clinical seizure frequency in patients with PVNH. Analysis of ictal ECoG records suggests PVNH may be involved in seizure generation. SignificanceChronic ECoG recordings suggest PVNH tissue can actively participate in epileptogenic networks. Direct brain-responsive neurostimulation is a safe and effective treatment option in such patients, progressively reducing seizure rate over a period of years.

Testing the Central Gain Model: Loudness Growth Correlates with Central Auditory Gain Enhancement in a Rodent Model of Hyperacusis

The central gain model of hyperacusis proposes that loss of auditory input can result in maladaptive neuronal gain increases in the central auditory system, leading to the over-amplification of sound-evoked activity and excessive loudness perception. Despite the attractiveness of this model, and supporting evidence for it, a critical test of the central gain theory requires that changes in sound-evoked activity be explicitly linked to perceptual alterations of loudness. Here we combined an operant conditioning task that uses a subject’s reaction time to auditory stimuli to produce reliable measures of loudness growth with chronic electrophysiological recordings from the auditory cortex and inferior colliculus of awake, behaviorally-phenotyped animals. In this manner, we could directly correlate daily assessments of loudness perception with neurophysiological measures of sound encoding within the same animal. We validated this novel psychophysical-electrophysiological paradigm with a salicylate-induced model of hearing loss and hyperacusis, as high doses of sodium salicylate reliably induce temporary hearing loss, neural hyperactivity, and auditory perceptual disruptions like tinnitus and hyperacusis. Salicylate induced parallel changes to loudness growth and evoked response-intensity functions consistent with temporary hearing loss and hyperacusis. Most importantly, we found that salicylate-mediated changes in loudness growth and sound-evoked activity were correlated within individual animals. These results provide strong support for the central gain model of hyperacusis and demonstrate the utility of using an experimental design that allows for within-subject comparison of behavioral and electrophysiological measures, thereby making inter-subject variability a strength rather than a limitation.

Plasticity changes in forebrain activity and functional connectivity during neuropathic pain development in rats with sciatic spared nerve injury

Neuropathic pain is a major worldwide health problem. Although central sensitization has been reported in well-established neuropathic conditions, information on the acute brain activation patterns in response to peripheral nerve injury is lacking. This study first mapped the brain activity in rats immediately following spared nerve injury (SNI) of the sciatic nerve. Using blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI), we observed sustained activation in the bilateral insular cortices (ICs), primary somatosensory cortex (S1), and cingulate cortex. Second, this study sought to link this sustained activation pattern with brain sensitization. Using manganese-enhanced magnetic resonance imaging (MEMRI), we observed enhanced activity in the ipsilateral anterior IC (AIC) in free-moving SNI rats on Days 1 and 8 post-SNI. Furthermore, enhanced functional connectivity between the ipsilateral AIC, bilateral rostral AIC, and S1 was observed on Day 8 post-SNI. Chronic electrophysiological recording experiments were conducted to confirm the tonic neuronal activation in selected brain regions. Our data provide evidence of tonic activation-dependent brain sensitization during neuropathic pain development and offer evidence that the plasticity changes in the IC and S1 may contribute to neuropathic pain development.

Long-term stability of neural signals from microwire arrays implanted in common marmoset motor cortex and striatum

Current neuroprosthetics rely on stable, high quality recordings from chronically implanted microelectrode arrays (MEAs) in neural tissue. While chronic electrophysiological recordings and electrode failure modes have been reported from rodent and larger non-human primate (NHP) models, chronic recordings from the marmoset model have not been previously described. The common marmoset is a New World primate that is easier to breed and handle compared to larger NHPs and has a similarly organized brain, making it a potentially useful smaller NHP model for neuroscience studies. This study reports recording stability and signal quality of MEAs chronically implanted in behaving marmosets. Six adult male marmosets, trained for reaching tasks, were implanted with either a 16-channel tungsten microwire array (five animals) or a Pt-Ir floating MEA (one animal) in the hand-arm region of the primary motor cortex (M1) and another MEA in the striatum targeting the nucleus accumbens (NAcc). Signal stability and quality was quantified as a function of array yield (active electrodes that recorded action potentials), neuronal yield (isolated single units during a recording session), and signal-to-noise ratio (SNR). Out of 11 implanted MEAs, nine provided functional recordings for at least three months, with two arrays functional for 10 months. In general, implants had high yield, which remained stable for up to several months. However, mechanical failure attributed to MEA connector was the most common failure mode. In the longest implants, signal degradation occurred, which was characterized by gradual decline in array yield, reduced number of isolated single units, and changes in waveform shape of action potentials. This work demonstrates the feasibility of long-term recordings from MEAs implanted in cortical and deep brain structures in the marmoset model. The ability to chronically record cortical signals for neural prosthetics applications in the common marmoset extends the potential of this model in neural interface research.

Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.

Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture.SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we performed chronic electrophysiological recordings of cortical neural activity during waking, sleep, and after sleep deprivation from young and older mice. We found that all main hallmarks of cortical activity during spontaneous sleep and recovery sleep after sleep deprivation were largely intact in older mice, suggesting that the well-described age-related changes in global sleep are unlikely to arise from a disruption of local network dynamics within the neocortex.

Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse

Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca2+ imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca2+ imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 μm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain.

Removal of Perineuronal Nets Unlocks Juvenile Plasticity Through Network Mechanisms of Decreased Inhibition and Increased Gamma Activity

Emerging evidence suggests a role for perineuronal nets (PNNs) in learning and regulation of plasticity, but the underlying mechanisms remain unresolved. Here, we used chronic in vivo extracellular recordings to investigate how removal of PNNs opens for plasticity and how activity-dependent plasticity affects neural activity over time. PNN removal caused reduced inhibitory activity and reset the network to a juvenile state. Experimentally induced activity-dependent plasticity by monocular deprivation caused rapid changes in single unit activity and a remarkable potentiation of gamma oscillations. Our results demonstrate how PNNs may be involved directly in stabilizing the neural network. Moreover, the immediate potentiation of gamma activity after plasticity onset points to potential new mechanisms for the initiation of activity-dependent plasticity.

Robust neuroprosthetic control from the stroke perilesional cortex.

Intracortical brain-machine interfaces (BMIs) may eventually restore function in those with motor disability after stroke. However, current research into the development of intracortical BMIs has focused on subjects with largely intact cortical structures, such as those with spinal cord injury. Although the stroke perilesional cortex (PLC) has been hypothesized as a potential site for a BMI, it remains unclear whether the injured motor cortical network can support neuroprosthetic control directly. Using chronic electrophysiological recordings in a rat stroke model, we demonstrate here the PLC's capacity for neuroprosthetic control and physiological plasticity. We initially found that the perilesional network demonstrated abnormally increased slow oscillations that also modulated neural firing. Despite these striking abnormalities, neurons in the perilesional network could be modulated volitionally to learn neuroprosthetic control. The rate of learning was surprisingly similar regardless of the electrode distance from the stroke site and was not significantly different from intact animals. Moreover, neurons achieved similar task-related modulation and, as an ensemble, formed cell assemblies with learning. Such control was even achieved in animals with poor motor recovery, suggesting that neuroprosthetic control is possible even in the absence of motor recovery. Interestingly, achieving successful control also reduced locking to abnormal oscillations significantly. Our results thus suggest that, despite the disrupted connectivity in the PLC, it may serve as an effective target for neuroprosthetic control in those with poor motor recovery after stroke.

A non-invasive head-holding device for chronic neural recordings in awake behaving monkeys

We have developed a novel head-holding device for behaving non-human primates that affords stability suitable for reliable chronic electrophysiological recording experiments. The device is completely non-invasive, and thus avoids the risk of infection and other complications that can occur with the use of conventional, surgically implanted head-fixation devices. The device consists of a novel non-invasive head mold and bar clamp holder, and is customized to the shape of each monkey's head. The head-holding device that we introduce, combined with our recording system and reflection-based eye-tracking system, allows for chronic behavioral experiments and single-electrode or multi-electrode recording, as well as manipulation of brain activity. With electrodes implanted chronically in multiple brain regions, we could record neural activity from cortical and subcortical structures with stability equal to that recorded with conventional head-post fixation. Consistent with the non-invasive nature of the device, we could record neural signals for more than two years with a single implant. Importantly, the monkeys were able to hold stable eye fixation positions while held by this device, demonstrating the possibility of analyzing eye movement data with only the gentle restraint imposed by the non-invasive head-holding device. We show that the head-holding device introduced here can be extended to the head holding of smaller animals, and note that it could readily be adapted for magnetic resonance brain imaging over extended periods of time.

From Hunger to Satiety: Reconfiguration of a Feeding Network byAplysiaNeuropeptide Y

A shift in motivational state often produces behavioral change, but the underlying mechanisms are poorly understood. In the marine mollusc, Aplysia californica, feeding-induced transition from a hunger to satiation state leads to a slowdown and an eventual termination of feeding. Because the multifunctional feeding network generates both ingestion and the competing response, egestion, it is possible that the transition from a hunger to a satiety state is associated with network reconfiguration that results in production of fewer ingestive and more egestive responses. Chronic electrophysiological recordings in free-feeding Aplysia showed that as the meal progressed, food elicited fewer ingestive responses and simultaneously increased the number of egestive responses. Injections of Aplysia neuropeptide Y (apNPY) reduced food intake and slowed down the rate of ingestion. apNPY was localized to buccal-ganglion afferents originating in the gut-innervating esophageal nerve (EN), a nerve involved both in satiation and in the generation of egestive programs. During EN stimulation, apNPY was released in the feeding circuit. Importantly, stimulation of the cerebral-buccal interneuron-2, a command-like interneuron that is activated by food and normally elicits ingestive responses, elicited egestive responses in the presence of apNPY. This was accompanied by increased activity of the egestion-promoting interneuron B20 and decreased activity in the ingestion-promoting interneuron B40. Thus, apNPYergic reconfiguration of the feeding central pattern generator plays a role in the gradual transition from hunger to satiety states. More generally, changes in the motivational states may involve not only simple network inhibition but may also require network reconfiguration.

Development of Neuronal Responsiveness in the Mediorostral Neostriatum/Hyperstriatum Ventrale during Auditory Filial Imprinting in Domestic Chicks

Chronic electrophysiological recordings of slow field potentials from tone-imprinted chicks show significantly enhanced fast Fourier transform (FFT) power during playback of rhythmic 400-Hz imprinting tone stimuli in the presence of a surrogate mother. The FFT power was already significantly higher during the very first imprinting session, when the chick was exposed to the imprinting tone stimuli in the presence of the surrogate mother compared to spontaneous activity (EEG recordings). During discrimination tests, where individual chicks were exposed to the imprinting tone stimuli in alternation to rhythmic 700-Hz tone stimuli (discrimination tone stimuli), the FFT power was significantly higher during playback of the imprinting tone stimuli than the FFT power during playback of the discrimination tone stimuli. Chicks which were imprinted in the absence of the surrogate mother also show enhanced FFT power in the course of the imprinting sessions; however, in contrast to the first group, they did not show significant differences in the FFT power during playback of either the imprinting or discrimination tone stimuli in the discrimination tests. Our results suggest that the high FFT power of a potential imprinting stimulus or situation, which is expressed in newborn (still naive) chicks, is maintained only when the chicks form an association between the tone stimuli and a positive emotional situation (represented by the surrogate mother).

Hypoxia-Induced Sleep Disturbance in Rats

The effects of varying degrees of hypoxia on sleep-wake organization were studied in rats prepared for chronic electrophysiological recording. The influence of Piracetam (75, 50, and 500 mg/kg, i.p.) and Hydergine (0.5, 1, and 3 mg/kg, i.p.) on sleep-wake organization in 10.5% oxygen was also investigated. The sleep-wake organization of rats under the effect of 15.5% oxygen content was unchanged, compared to that of normoxic control. More extreme hypoxia (12.6 and 10.5% oxygen) produced dramatic changes in sleep organization without influencing gross behavior. Paradoxical sleep (PS) stages became less frequent and shortened and were totally absent in 10.5% oxygen. Frequent wakings caused disturbed and superficial sleep. Central biochemical mechanisms, peripheral chemoreceptor reflex pathways and, as a consequence, decrease of duration of deep sleep periods, may contribute to the development of hypoxic sleep disturbances. Piracetam alleviated and Hydergine moderately reversed the hypoxic sleep disturbance.

Neuropharmacological and electrophysiological evidence implicating the mesolimbic dopamine system in feeding responses elicited by electrical stimulation of the medial forebrain bundle

The contribution of the mesolimbic dopamine pathway to feeding behavior was investigated in rats in which feeding responses were elicited by electrical stimulation of the medial forebrain bundle at the level of the lateral hypothalamus. Injections of spiroperidol, a dopamine antagonist, into the nucleus accumbens ipsilateral to the stimulating electrode significantly attenuated the elicited feeding responses whereas injecting spiroperidol into the contralateral nucleus accumbens had no effect. The spontaneous discharge rates of neurons of the ventral tegmental area, identified by their electrophysiological characteristics as dopaminergic, were both increased and decreased in response to single pulse stimulation of sites in the medial forebrain bundle from which feeding responses had been elicited. These observations suggest that mesolimbic dopaminergic neurons may have a role in feeding behavior and indicate the need for chronic electrophysiological recording experiments to see whether or not the activity of these neurons is correlated with the initiation of elicited and spontaneous feeding responses.