Behavioral Arrest Research Articles

Muscimol injection into the substantia nigra but not globus pallidus affects prepulse inhibition and startle reflex.

Behavioral arrest is an essential feature of an animal's survival. Acoustic startle reflex (ASR) is an involuntary whole-body contraction of the skeletal musculature to an unexpected auditory stimulus. This strong reaction can be decreased by prepulse inhibition (PPI) phenomenon; which, for example, is important in reducing distraction during the processing of sensory input. Several brainstem regions are involved in the PPI and startle reflex, but a previous study from our laboratory showed that the main input structure of Basal Ganglia (BG) – the striatum – modulates PPI. The pallidum and nigra are connected with striatum and these brainstem structures. Here, we investigated the role of these striatum outputs in the brain regions on startle amplitude, PPI regulation, and exploratory behavior in Wistar rats. The temporary bilateral inhibition of the globus pallidus (GP) by muscimol lead to motor impairment, without disturbing startle amplitude or PPI. Similarly, inhibition of the entopeduncular nucleus (EPN) specifically disrupted the exploratory behavior. On the other hand, the substantia nigra reticulata (SNr) inhibition interfered in all measured behaviors: decreased the PPI percentage, increased ASR and impaired the locomotor activity. The nigra is a key BG output structure which projects to the thalamus and brainstem. These findings extend our previous study showing that the striatum neurons expressing D1 receptors involvement in PPI occurs via the direct pathway to SNr, but not to the pallidum which more likely occurs by its connection with the caudal pontine nucleus, superior colliculus and/or pedunculopontine nucleus pivotal structures for startle reflex modulation.

The impact of silencing feed-forward parvalbumin-expressing inhibitory interneurons in the cortico-thalamocortical network on seizure generation and behaviour

Feed-forward inhibition (FFI) is an essential mechanism within the brain, to regulate neuronal firing and prevent runaway excitation. In the cortico-thalamocortical (CTC) network, fast spiking parvalbumin-expressing (PV+) inhibitory interneurons regulate the firing of pyramidal cells in the cortex and relay neurons in the thalamus. PV+ interneuron dysfunction has been implicated in several neurological disorders, including epilepsy. Previously, we demonstrated that loss of excitatory AMPA-receptors, specifically at synapses on PV+ interneurons in CTC feedforward microcircuits, occurs in the stargazer mouse model of absence epilepsy. These mice present with absence seizures characterized by spike and wave discharges (SWDs) on electroencephalogram (EEG) and concomitant behavioural arrest, similar to childhood absence epilepsy. The aim of the current study was to investigate the impact of loss of FFI within the CTC on absence seizure generation and behaviour using new Designer Receptor Exclusively Activated by Designer Drug (DREADD) technology. We crossed PV-Cre mice with Cre-dependent hM4Di DREADD strains of mice, which allowed Cre-recombinase-mediated restricted expression of inhibitory Gi-DREADDs in PV+ interneurons. We then tested the impact of global and focal (within the CTC network) silencing of PV+ interneurons. CNO mediated silencing of all PV+ interneurons by intraperitoneal injection caused the impairment of motor control, decreased locomotion and increased anxiety in a dose-dependent manner. Such silencing generated pathological oscillations similar to absence-like seizures. Focal silencing of PV+ interneurons within cortical or thalamic feedforward microcircuits, induced SWD-like oscillations and associated behavioural arrest. Epileptiform activity on EEG appeared significantly sooner after focal injection compared to peripheral injection of CNO. However, the mean duration of each oscillatory burst and spike frequency was similar, irrespective of mode of CNO delivery. No significant changes were observed in vehicle-treated or non-DREADD wild-type control animals. These data suggest that dysfunctional feed-forward inhibition in CTC microcircuits may be an important target for future therapy strategies for some patients with absence seizures. Additionally, silencing of PV+ interneurons in other brain regions may contribute to anxiety related neurological and psychiatric disorders.

Spontaneous Recurrent Absence Seizure-like Events in Wild-Caught Rats.

Absence epilepsy is a heritable human neurological disorder characterized by brief nonconvulsive seizures with behavioral arrest, moderate-to-severe loss of consciousness (absence), and distinct spike-wave discharges (SWDs) in the EEG and electrocorticogram (ECoG). Genetic models of this disorder have been created by selectively inbreeding rats for absence seizure-like events with similar electrical and behavioral characteristics. However, these events are also common in outbred laboratory rats, raising concerns about whether SWD/immobility accurately reflects absence epilepsy as opposed to "normal" rodent behavior. We hypothesized that, if SWD/immobility models absence seizures, it would not exist in wild-caught rats due to the pressures of natural selection. To test this hypothesis, we compared chronic video/electrocorticogram recordings from male and female wild-caught (Brown-Norway [BN]) rats to recordings from laboratory outbred BN, outbred Long-Evans, and inbred WAG/Rij rats (i.e., a model of absence epilepsy). Wild-caught BN rats displayed absence-like SWD/immobility events that were highly similar to outbred BN rats in terms of spike-wave morphology, frequency, diurnal rhythmicity, associated immobility, and sensitivity to the anti-absence drug, ethosuximide; however, SWD bursts were less frequent and of shorter duration in wild-caught and outbred BN rats than the outbred Long-Evans and inbred WAG/Rij strains. We conclude that SWD/immobility in rats does not represent absence seizures, although they appear to have many similarities. In wild rats, SWD/immobility appears to represent normal brain activity that does not reduce survival in natural environments, a conclusion that logically extends to outbred laboratory rats and possibly to those that have been inbred to model absence epilepsy.SIGNIFICANCE STATEMENT Spike-wave discharges (SWDs), behavioral arrest, and diminished consciousness are cardinal signs of seizures in human absence epilepsy and are used to model this disorder in inbred rats. These characteristics, however, are routinely found in outbred laboratory rats, leading to debate on whether SWD/immobility is a valid model of absence seizures. The SWD/immobility events in wild-caught rats appear equivalent to those found in outbred and inbred rat strains, except for lower incidence and shorter durations. Our results indicate that the electrophysiological and behavioral characteristics of events underlying hypothetical absence epilepsy in rodent models are found in wild rats captured in their natural environment. Other criteria beyond observation of SWDs and associated immobility are required to objectively establish absence epilepsy in rat models.

Epileptological aspects of juvenile neuronal ceroid lipofuscinosis (CLN3 disease) through the lifespan

PurposeJuvenile neuronal ceroid lipofuscinosis (CLN3 disease) is the most common neurodegenerative disorder in childhood with survival until young adult age. Visual loss is followed by epilepsy, cognitive, neuropsychiatric, and motor symptoms. We have studied the evolution of electroencephalographic (EEG) and seizure characteristics. MethodsTwenty-four patients were recruited via the Norwegian CLN3 disease parent association. Parents were interviewed. Medical records and EEG reports/recordings were collected. Electroencephalographic elements were classified according to Standardized computer-based organized reporting of EEG (SCORE). The evolution of EEG features along with seizure types was assessed by testing the difference in proportions with standardized normal deviate comparing findings below and above 15 years of age. ResultsMean age at study or death (n = 12) was 21.2 (10–39) years. Twenty-two patients had experienced seizures; the first was usually bilateral tonic–clonic (TC). Later, focal motor seizures frequently occurred, often with increasing multifocal and polymorphic features. Paroxysmal nonepileptic motor and autonomous symptoms were also suspected in several patients. Distinct myoclonic seizures were uncommon. In four patients, we identified episodes of bradycardia/sinus arrest. Electroencephalography showed progressive slowing of the background activity (p = 0.029). Focal epileptiform discharges were rare and mainly seen at age <10. Combined multifocal and bilateral epileptiform discharges increased in adolescence (p = 0.002). ConclusionSeizure and EEG characteristics change with time in CLN3 disease. Tonic–clonic seizures are common at onset, and multifocal motor seizures increase with age. In contrast, focal epileptiform abnormalities are more common in childhood, compared to later multifocal and bilateral discharges. This seizure disorder belongs to the combined generalized and focal epilepsies. Paucity of myoclonic seizures does not warrant classification as a classic progressive myoclonic epilepsy. When attacks with only behavior arrest occur, cardiac conduction abnormalities should be considered.

Insights on the Role of Thalamocortical HCN Channels in Absence Epilepsy.

Absence epilepsy is the most common type of epilepsy in childhood ([Glauser et al., 2010][1]). It is characterized by sudden, transient loss of consciousness, behavioral arrest, and an EEG pattern dominated by spike-and-wave discharges ([Crunelli and Leresche, 2002][2]). Through studies performed on

Abstract #114: Rapidly reversible behavioral arrest during fasciculus retroflexus deep brain stimulation in a healthy non-human primate

Abstract #114: Rapidly reversible behavioral arrest during fasciculus retroflexus deep brain stimulation in a healthy non-human primate

Loss of HCN1 subunits causes absence epilepsy in rats

Hyperpolarized-activated cyclic nucleotide-gated (HCN) channels underlie hyperpolarization-activated current (Ih) and are involved in controlling the excitability and electrical responsiveness of neurons. Absence epilepsy is clinically defined by a sudden, brief impairment of consciousness and behavioral arrest. Spike-and-wave discharges (SWDs) on electroencephalograms (EEG) are a diagnostic hallmark of absence epilepsy. In rat models of absence epilepsy, impaired function or expression of HCN1, a subtype of HCN channels, has been found. Here, to evaluate whether HCN1 deficiency causes absence epilepsy in rats, we developed Hcn1-knockout rats by transcription activator-like effector nuclease mutagenesis. The cortical and hippocampal pyramidal neurons of these rats displayed a significant reduction of Ih, a pronounced hyperpolarizing shift of the resting membrane potential, and increased input resistance, which indicated that the Hcn1-knockout rats were deficient in HCN1 function. The Hcn1-knockout rats were also more vulnerable to pentylenetetrazol-induced acute convulsions. More importantly, they exhibited spontaneous SWDs, which were accompanied by behavioral arrest, both of which were suppressed by ethosuximide. These results confirm the involvement of the HCN1 subunit in the regulation of input resistance and provide direct evidence that a deficiency of HCN1 caused absence epilepsy in rats.

Distinguishing Subtypes of Mutual Violence in the Context of Self-defense: Classifying Types of Partner Violent Couples using a Modified Conflict Tactics Scale.

The Revised Conflict Tactics Scale 2 (CTS2; Straus, Hamby, Boney-McCoy, & Sugarman, 1996) is the most widely used measure for assessing the frequency of intimate partner violence (IPV). However, it has been criticized for not capturing the context in which IPV takes place. This study examined follow-up items to each CTS2 physical assault item asking to clarify how often the act was perpetrated in self-defense. A community sample of couples (N = 180) recruited for men's recent violence toward women completed the project-modified Conflict Tactics Scale with Self-Defense (CTS2SD). The majority (69.5%) reported that the physical aggression in the past year was bilateral. On the follow-up items, 27% of men's violent acts and over 22% of women's violent acts were reportedly committed in self-defense. Men's and women's CTS2 physical assault perpetration scores, along with the percentage that were committed in self-defense, were entered into two-step cluster analyses. Cluster analyses revealed three subgroups of bilateral violence: Male Self-defense, Female Self-defense, and Mutual Violence. The Mutual Violent cluster reported the most frequent physical assault, injury, men's controlling behavior and men's arrest for domestic violence. Findings suggest that Straus' (2012) tripartite conceptualization of Man-only, Woman-only, and Both-violent couples is overly simplistic and fails to capture different types of bilateral aggression.

Development of propagated discharge and behavioral arrest in hippocampal and amygdala-kindled animals

Patients with focal temporal lobe seizures often experience transient episodes of impaired awareness with behavioral arrest, but the precise mechanism remains unknown. The Network Inhibition Hypothesis attributes these deficits to a loss of cholinergic input to the cortex. This is presumed to result from increased activation of inhibitory regions that suppress subcortical arousal, giving rise to cortical delta wave activity. Recently, this hypothesis has been tested in animal experiments, where triggering dorsal hippocampal seizures is associated with behavioral arrest. To further test this hypothesis in animals – and, more specifically, to characterize the relationship between propagated discharge, cortical delta waves and behavioral arrest – we performed partial kindling studies in three different limbic sites in rats. We found that seizure discharge took longer to spread from the amygdala than the hippocampus, and took more stimulations to elicit behavioral arrest. In addition, the onset of propagated discharge in subcortical and cortical sites did not always match with the onset of behavioral arrest. Importantly, the activity seen in the cortex did not resemble the slow waves seen in deep sleep. Together, these findings suggest that limbic discharge triggers epileptic discharge in downstream pacemakers, including the cortex, and that these secondarily cause behavioral arrest.

Impact of strain, sex, and estrous cycle on gamma butyrolactone-evoked absence seizures in rats

Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome and is characterized by typical absence seizures (AS). AS are non-convulsive epileptic seizures characterized by a sudden loss of awareness and bilaterally generalized synchronous 2.5–4 Hz spike and slow-wave discharges (SWD). Gamma butyrolactone (GBL) is an acute pharmacological model of AS and induces bilaterally synchronous SWDs and behavioral arrest. Despite the long use of this model, little is known about its strain and sex-dependent features. We compared the dose-response profile of GBL-evoked SWDs in three rat strains (Long Evans, Sprague-Dawley, and Wistar), and examined the modulatory effects of estrous cycle on SWDs in female Wistar rats. We evaluated the number of seizures, the cumulative time seizing, and the average seizure duration as a function of dose, strain, and sex/estrous phase. Long Evans rats displayed the greatest sensitivity to GBL, followed by Wistar rats, and then by Sprague-Dawley rats. GBL-evoked SWDs were modulated by estrous cycle in female rats, with the lowest sensitivity to GBL occurring during metestrus. Wistar rats showed the greatest variability as a function of dose, and the least variability within dose; these features make this strain desirable for interventional studies. Moreover, our finding that the SWD response to GBL differs as a function of estrous cycle underscores the importance of cycle monitoring in studies examining female animals using this model. Together, these strain and sex-dependent findings provide guidance for future studies.

1. The development of propagated discharge and behavioural arrest in hippocampal and amygdala kindled seizures

Patients with focal temporal lobe seizures often experience transient episodes of impaired awareness with behavioural arrest, but the precise mechanism remains unknown. The Blumenfeld hypothesis attributes these deficits to a loss of cholinergic input to the cortex. This is presumed to result from increased activation of inhibitory regions that suppress subcortical arousal, giving rise to slow wave activity. To investigate this hypothesis – and more specifically, to characterize the relationship between propagated discharge, cortical slow waves and behavioural arrest – we performed kindling studies in rats. We found that seizure discharge took longer to spread from the amygdala than the hippocampus, and took more kindling stimulations to elicit behavioural arrest. In addition, the onset of propagated discharge in subcortical and cortical sites did not always match with the onset of behavioural arrest. Importantly, the activity seen in the cortex did not resemble the slow waves seen in deep sleep. Together, these findings suggest an additional mechanism – other than the Blumenfeld hypothesis – to explain how temporal lobe seizures may produce behavioural arrest and impair awareness.

Ictal signs in tuberous sclerosis complex: Clinical and video-EEG features in a large series of recorded seizures

Epilepsy is the most common neurological symptom in tuberous sclerosis complex (TSC), occurring in 72–85% of affected individuals. Despite the large number of patients reported, their electroclinical phenotype has been rarely described. We analyzed seizure semiology through ictal video-electroencephalography (V-EEG) recordings in a large series of patients. In this multicenter study, we reviewed V-EEGs of 51 patients: ictal recordings were analyzed in correlation with their clinical variables.The median age of epilepsy onset was six months (one day–16 years), with onset in the first year of life in 71% patients (36/51), in 10 of them during the neonatal period. Sixty-five percent of patients (33/51) experienced epileptic spasms in their life, with late-onset (>two years) in five; 42% of the epileptic spasms persisted after age two years, despite the onset in the first year of life.We identified four different electroclinical subsets: focal epilepsy (35%, 18/51), Lennox–Gastaut Syndrome evolution (27%, 14/51), focal seizures with persisting spasms (33%, 17/51), and spasms only (4%, 2/51).We reviewed 45 focal seizures, 13 clusters of epileptic spasms, and seven generalized seizures. In 12 patients, we recorded different seizure types. In 71% of the focal seizures (32/45), the ictal pattern was focal without diffusion. In 38% of the patients (5/13) epileptic spasms were related to typical diffuse slow wave pattern associated with superimposed fast activity, with focal predominance.Focal seizures and focal spasms resulted as the most frequent seizure types in TSC. Seizure onset was variable but showing a predominant involvement of the frontocentral regions (40%). Discrete clinical signs characterized the seizures, and behavioral arrest was the predominant first clinical objective sign. Epileptic spasms were a typical presentation at all ages, frequently asymmetrical and associated with lateralizing features, especially in older patients.

Clinical and electrographic presentation of a case of hemimegalencephaly

Objectives Epilepsy is a common and potentially serious and disabling disease. Congenital malformations of the brain are often associated with severe presentations and difficult drug control. Our objective is to report a case of a child with hemimegalencephaly, the clinical and electroencephalographic presentation before and after neurosurgery. Methods RAR, a 2-year-old girl with difficult-to-control epilepsy using a combination of high doses of anticonvulsants, presented daily crisis from the neonatal period. She was monitored with video-EEG before and after brain surgery. Clinical presentation and electroencephalographic changes helped to indicate the procedure. Results The video-EEG showed crises characterized by behavioral arrest, eyes up and stillness. Inter-ictal EEG had continuous poly-spykes in the right hemisphere and focal EEG accentuates epileptiform activity over the right quadrant region. Magnetic resonance imaging of the requested brain with right hemimegalencephaly. The patient underwent right hemispherectomy in December 2017, provided no recurrence of crisis. Her behavior and development is also better. She will be admitted shortly for a new video-EEG monitoring. Conclusion Hemimegalencephaly is a malformation of cortical development characterized by excessive hamartomatous growth of all or part of a cerebral hemisphere and frequently associated with refractory epilepsy. Patients may present with early encephalopathy, delayed neuropsychomotor development, motor deficits and learning disabilities. Anatomic or functional hemispherectomy is indicated if epilepsy is clinically intractable.

Structural organisation and dynamics in king penguin colonies

During breeding, king penguins do not build nests, however they show strong territorial behaviour and keep a pecking distance to neighbouring penguins. Penguin positions in breeding colonies are highly stable over weeks and appear regularly spaced, but thus far no quantitative analysis of the structural order inside a colony has been performed. In this study, we use the radial distribution function to analyse the spatial coordinates of penguin positions. Coordinates are obtained from aerial images of two colonies that were observed for several years. Our data demonstrate that the structural order in king penguin colonies resembles a 2D liquid of particles with a Lennard-Jones-type interaction potential. We verify this using a molecular dynamics simulation with thermally driven particles, whereby temperature corresponds to penguin movements, the energy well depth ϵ of the attractive potential corresponds to the strength of the colony-forming behaviour, and the repulsive zone corresponds to the pecking radius. We can recapitulate the liquid disorder of the colony, as measured by the radial distribution function, when the particles have a temperature of several (1.4–10) and a normally distributed repulsive radius. To account for the observation that penguin positions are stable over the entire breeding period, we hypothesize that the liquid disorder is quenched during the colony formation process. Quenching requires the temperature to fall considerably below 1 , which corresponds to a glass transition, or the repulsion radius to exceed the distance between neighbouring penguins, which corresponds to a jamming transition. Video recordings of a breeding colony together with simulations suggest that quenching is achieved by a behavioural motility arrest akin to a glass transition. We suggest that a liquid disordered colony structure provides an ideal compromise between high density and high flexibility to respond to external disturbances that require a repositioning of penguins.

POISONED DEVELOPMENT: ASSESSING CHILDHOOD LEAD EXPOSURE AS A CAUSE OF CRIME IN A BIRTH COHORT FOLLOWED THROUGH ADOLESCENCE

AbstractThe consequences of lead exposure for later crime are theoretically compelling, but direct evidence from representative, longitudinal samples is sparse. By capitalizing on an original follow‐up of more than 200 infants from the birth cohort of the Project on Human Development in Chicago Neighborhoods matched to their blood lead levels from around age 3 years, we provide several tests. Through the use of four waves of longitudinal data that include measures of individual development, family background, and structural inequalities in how lead becomes embodied, we assess the hypothesized link between early childhood lead poisoning and both parent‐reported delinquent behavior and official arrest in late adolescence. We also test for mediating developmental processes of impulsivity and anxiety or depression. The results from multiple analytic strategies that make different assumptions reveal a plausibly causal effect of childhood lead exposure on adolescent delinquent behavior but no direct link to arrests. The results underscore lead exposure as a trigger for poisoned development in the early life course and call for greater integration of the environment into theories of individual differences in criminal behavior.

Semiology, clustering, periodicity and natural history of seizures in an experimental occipital cortical epilepsy model.

ABSTRACTFocal neocortical epilepsy is a common form of epilepsy and there is a need to develop animal models that allow the evaluation of novel therapeutic strategies to treat this type of epilepsy. Tetanus toxin (TeNT) injection into the rat visual cortex induces focal neocortical epilepsy without preceding status epilepticus. The latency to first seizure ranged from 3 to 7 days. Seizure duration was bimodal, with both short (approximately 30 s) and long-lasting (>100 s) seizures occurring in the same animals. Seizures were accompanied by non-motor features such as behavioural arrest, or motor seizures with or without evolution to generalized tonic-clonic seizures. Seizures were more common during the sleep phase of a light-dark cycle. Seizure occurrence was not random, and tended to cluster with significantly higher probability of recurrence within 24 h of a previous seizure. Across animals, the number of seizures in the first week could be used to predict the number of seizures in the following 3 weeks. The TeNT model of occipital cortical epilepsy is a model of acquired focal neocortical epilepsy that is well-suited for preclinical evaluation of novel anti-epileptic strategies. We provide here a detailed analysis of the epilepsy phenotypes, seizure activity, electrographic features and the semiology. In addition, we provide a predictive framework that can be used to reduce variation and consequently animal use in preclinical studies of potential treatments.

Locomotor speed control circuits in the caudal brainstem.

Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs.

Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats.

Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs) within the prefrontal cortex (PFC), parietal cortex (PC), and central thalamus (CT) in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12–40 Hz) power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC–CT and PFC–PFC LFP beta/low gamma coherence increased. Loss of movement (LOM) coincided with an abrupt decrease in beta/low gamma PFC–CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1–4 Hz) oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats.

Short-term deep brain stimulation of the thalamic reticular nucleus modifies aberrant oscillatory activity in a neurodevelopment model of schizophrenia

Dysfunction of thalamo-cortical networks involving particularly the thalamic reticular nucleus (TRN) is implicated in schizophrenia. In the neonatal ventral hippocampal lesion (NVHL), a heuristic animal model of schizophrenia, brain oscillation changes similar to those of schizophrenic patients have been reported. The aim of this study was to analyze the effects of short-term deep brain stimulation (DBS) in the thalamic reticular nucleus on electroencephalographic (EEG) activity in the NVHL. Male and female Sprague–Dawley rats were used and the model was prepared by excitotoxicity damage of the ventral hippocampus on postnatal day 7 (PD-7). Chronic bilateral stainless steel electrodes were implanted in the TRN, thalamic dorsomedial nucleus and prelimbic area at PD-90. Rats were classified as follows: sham and NVHL groups, both groups received bilateral DBS in the TRN for one hour (100Hz, 100µs pulses, 200µA). All animals showed a sudden behavioral arrest accompanied by widespread symmetric bilateral spike–wave discharges, this activity was affected by DBS-TRN. Additionally, the power spectra of 0.5–100Hz and the coherence of 0.5–4.5 and 35–55Hz frequencies were modified by DBS-TRN. Our results suggest that DBS in the TRN may modify functional connectivity between different parts of the thalamo-cortical network. Additionally, our findings may suggest a beneficial effect of DBS-TRN on some preclinical aberrant oscillatory activities in a neurodevelopmental model of schizophrenia.

Parachlorophenylalanine-induced 5-HT depletion alters behavioral and brain neurotransmitters levels in 6-Hz psychomotor seizure model in mice.

The present study was designed to investigate the role of serotonin and other neurotransmitters namely dopamine (DA), histamine, nor-epinephrine (NE), glutamate, and γ-aminobutyric acid (GABA) in the 6-Hz-induced psychomotor seizures in Swiss albino mice. Parachlorophenylalanine (PCPA, 300 mg/kg/day, i.p for 3 days)-treated mice were given 6-Hz stimulation. Sodium valproate (SVP) (200 mg/kg/day, p.o for 3 days) was used as a reference antiepileptic drug. The behavioral changes induced by 6 Hz including increased rearing and grooming, Straub's tail, behavioral arrest, stun position were amplified by PCPA. The 6-Hz-induced seizures were accompanied by reduced brain 5-HT, DA, NE, histamine, GABA, and enhanced glutamate levels. PCPA facilitated further reduction of endogenous 5-HT and DA levels but not NE, histamine, GABA, and glutamate levels. Pre- and post-treatment with SVP protected the mice from 6-Hz seizures and attenuated PCPA-induced changes in the levels of 5-HT and DA in the mice brain suggesting the protective effect of SVP in the pharmacoresistant model of epilepsy involving mainly serotonergic mechanism. However, the study also suggests modulation of other neurotransmitters both in 6-Hz psychomotor seizures and in the action of SVP against such seizures.