Thinking about the nerve impulse: A critical analysis of the electricity-centered conception of nerve excitability.

Nerve impulse generation and propagation are often thought of as solely electrical events. The prevalence of this view is the result of long and intense study of nerve impulses in electrophysiology culminating in the introduction of the Hodgkin-Huxley model of the action potential in the 1950s. To this day, this model forms the physiological foundation for a broad area of neuroscientific research.

Heterogeneous neuronal activity in the lateral habenula after short- and long-term cocaine self-administration in rats.

Cocaine addiction is thought to be the result of drug-induced functional changes in a neural network implicated in emotions, learning and cognitive control. Recent studies have implicated the lateral habenula (LHb) in drug-directed behavior, especially its aversive aspects. Limited cocaine exposure has been shown to alter neuronal activity in the LHb, but the impact of long-term drug exposure on habenula function has not been determined.

Alterations in Functional Cortical Hierarchy in Hemiparkinsonian Rats.

Parkinson's disease and experimentally induced hemiparkinsonism are characterized by increased beta synchronization between cortical and subcortical areas. This change in beta connectivity might reflect either a symmetric increase in interareal influences or asymmetric changes in directed influences among brain areas. We assessed patterns of functional and directed connectivity within and between striatum and six cortical sites in each hemisphere of the hemiparkinsonian rat model.

A neuronal activation correlate in striatum and prefrontal cortex of prolonged cocaine intake.

Maladaptive changes in the involvement of striatal and frontal cortical regions in drug use are thought to underlie the progression to habitual drug use and loss of cognitive control over drug intake that occur with accumulating drug experience. The present experiments focus on changes in neuronal activity in these regions associated with short-term (10 days) and long-term (60 days) self-administration of cocaine. Quantitative in situ hybridization for the immediate early gene Mkp1 was combined with statistical parametric mapping to assess the distribution of neuronal activity.

Postmortem validation of MRI cortical volume measurements in MS.

Grey matter (GM) atrophy is a prominent aspect of multiple sclerosis pathology and an important outcome in studies. GM atrophy measurement requires accurate GM segmentation. Several methods are used in vivo for measuring GM volumes in MS, but assessing their validity in vivo remains challenging.

Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration.

The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long-term drug self-administration.

Neuronal and axonal loss in normal-appearing gray matter and subpial lesions in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the CNS. Multiple sclerosis lesions include significant demyelination of the gray matter, which is thought to be a major contributor to both physical and cognitive impairment. Subpial (Type III) lesions are the most common demyelinated cortical lesions.

Pharmacological inactivation of the prelimbic cortex emulates compulsive reward seeking in rats.

Drug addiction is a chronic, relapsing brain disorder characterized by compulsive drug use. Contemporary addiction theories state that loss of control over drug use is mediated by a combination of several processes, including a transition from goal-directed to habitual forms of drug seeking and taking, and a breakdown of the prefrontally-mediated cognitive control over drug intake. In recent years, substantial progress has been made in the modelling of loss of control over drug use in animal models, but the neural substrates of compulsive drug use remain largely unknown.

Using conditioned suppression to investigate compulsive drug seeking in rats.

Background: Persistent drug seeking despite harmful consequences is a defining characteristic of addiction. Recent preclinical studies have demonstrated the occurrence of this hallmark feature of addictive behaviour in rodents. For example, it has been shown that the ability of an aversive conditioned stimulus (CS) to suppress cocaine seeking was diminished after an extended self-administration history.

Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease.

To gain a better understanding of the significance of α-synuclein pathological conditions during disease progression in Parkinson's disease, we investigated whether 1) nigral neuronal loss in incidental Lewy body disease and Parkinson's disease donors is associated with the local burden α-synuclein pathological conditions during progression of pathological conditions; 2) the burden and distribution of α-synuclein pathological conditions are related to clinical measures of disease progression. Post-mortem tissue and medical records of 24 Parkinson's disease patients, 20 incidental Lewy body disease donors, and 12 age-matched controls were obtained from the Netherlands Brain Bank for morphometric analysis. We observed a 20% decrease in nigral neuronal cell density in incidental Lewy body disease compared with controls.

Reduced dopamine transporter binding predates impulse control disorders in Parkinson's disease.

Impulse control disorders (ICD) are relatively common in Parkinson's disease (PD) and generally are regarded as adverse effects of dopamine replacement therapy, although certain demographic and clinical risk factors are also involved. Previous single-photon emission computed tomography (SPECT) studies showed reduced ventral striatal dopamine transporter binding in Parkinson patients with ICD compared with patients without. Nevertheless, these studies were performed in patients with preexisting impulse control impairments, which impedes clear-cut interpretation of these findings.

Acute administration of haloperidol does not influence 123I-FP-CIT binding to the dopamine transporter.

Unlabelled: A recent (123)I-FP-CIT ((123)-I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) SPECT study on rats suggested that a single 1 mg/kg dose of the antipsychotic haloperidol induces enough dopamine release to compete with (123)I-FP-CIT for binding to the dopamine transporter. Taking into account the far-reaching consequences of this proposition, we were interested in testing whether we could reproduce this finding using storage phosphor imaging.

Methods: Twenty rats were pretreated with saline or haloperidol (1 mg/kg of body weight) and then injected with (123)I-FP-CIT.

Decreased ipsilateral [¹²³I]iododexetimide binding to cortical muscarinic receptors in unilaterally 6-hydroxydopamine lesioned rats.

Introduction: Dysfunction of the cholinergic neurotransmitter system is present in Parkinson's disease, Parkinson's disease related dementia and dementia with Lewy bodies, and is thought to contribute to cognitive deficits in these patients. In vivo imaging of the cholinergic system in these diseases may be of value to monitor central cholinergic disturbances and to select cases in which treatment with cholinesterase inhibitors could be beneficial. The muscarinic receptor tracer [(123)I]iododexetimide, predominantly reflecting M1 receptor binding, may be an appropriate tool for imaging of the cholinergic system by means of SPECT.

Depression and impulse control disorders in Parkinson's disease: two sides of the same coin?

Depression and impulse control disorders (ICD) are two common neuropsychiatric features in Parkinson's disease (PD). Studies have revealed that both phenomena are associated with aberrations in ventral striatal dopamine signaling and concomitant dysfunction of the reward-related (limbic) cortico-striatal-thalamocortical (CSTC) circuit. Depression in PD seems associated with decreased activity in the limbic CSTC circuit, whereas ICD seem associated with increased limbic CSTC circuit activity, usually after commencing dopamine replacement therapy (DRT).

Functional integrity of the habenula is necessary for social play behaviour in rats.

During post-weaning development, a marked increase in peer-peer interactions is observed in mammals, including humans, which is signified by the abundance of social play behaviour. Social play is highly rewarding, and known to be modulated through monoaminergic neurotransmission. Recently, the habenula has received widespread attention because of its role in the regulation of monoaminergic neurotransmission as well as in a variety of emotional and cognitive functions.

Cellular activation in limbic brain systems during social play behaviour in rats.

Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited.

Density gradients of vesicular glutamate- and GABA transporter-immunoreactive boutons in calbindinand μ-opioid receptor-defined compartments in the rat striatum.

Cortical and subcortical inputs to the striatum are functionally highly organized and they obey to some extent striatal patch-matrix topography. Whether this organization is reflected in the density of various glutamatergic endings is unknown. We therefore mapped boutons expressing the vesicular glutamate transporters VGluT1 and VGluT2, together with boutons immunoreactive for vesicular γ-aminobutyric acid (GABA) transporter (VGAT) in patch and matrix throughout the striatum.

Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-delta.

A main neurogenic niche in the adult human brain is the subventricular zone (SVZ). Recent data suggest that the progenitors that are born in the human SVZ migrate via the rostral migratory stream (RMS) towards the olfactory bulb (OB), similar to what has been observed in other mammals. A subpopulation of astrocytes in the SVZ specifically expresses an assembly-compromised isoform of the intermediate filament protein glial fibrillary acidic protein (GFAP-delta).

Corticostriatal Interactions during Learning, Memory Processing, and Decision Making.

This mini-symposium aims to integrate recent insights from anatomy, behavior, and neurophysiology, highlighting the anatomical organization, behavioral significance, and information-processing mechanisms of corticostriatal interactions. In this summary of topics, which is not meant to provide a comprehensive survey, we will first review the anatomy of corticostriatal circuits, comparing different ways by which "loops" of cortical-basal ganglia circuits communicate. Next, we will address the causal importance and systems-neurophysiological mechanisms of corticostriatal interactions for memory, emphasizing the communication between hippocampus and ventral striatum during contextual conditioning.

Dynorphin displaces binding at the glycine site of the NMDA receptor in the rat striatum.

Binding of dynorphin A (1-17 and 2-17) to NMDA receptors in the rat striatum was studied by displacing radioactive ligands for the receptor's polyamine ([3H]-Ifenprodil), glutamate ([3H]-CGP-39653), dizocilpine ([3H]-MK-801) and glycine ([3H]-MDL105,519) sites with the neuropeptide. Dynorphin A selectively displaced [3H]-MDL105,519 and none of the other ligands. Opioid antagonists did not affect displacement.

Enhanced cortical and accumbal molecular reactivity associated with conditioned heroin, but not sucrose-seeking behaviour.

Re-exposure to drug-related cues elicits drug-seeking behaviour and relapse in both humans and laboratory animals even after months of abstinence. Identifying neural and molecular substrates underlying conditioned heroin-seeking behaviour will be helpful in understanding mechanisms behind opiate relapse. In humans and animals, brain areas activated by natural reward-related stimuli (e.

Differential involvement of the prelimbic cortex and striatum in conditioned heroin and sucrose seeking following long-term extinction.

Relapse to drug taking is triggered by stimuli previously associated with consumption of drugs of misuse (cues) and involves brain systems controlling motivated behaviour towards natural reinforcers. In this study, we aimed to identify and compare neuronal pathways in corticostriatal systems that control conditioned heroin or natural reward (sucrose) seeking. To that end, rats were trained to self-administer heroin or sucrose in association with an identical compound cue.

Molecular reactivity of mesocorticolimbic brain areas of high and low grooming rats after elevated plus maze exposure.

High and low grooming rats (HG and LG), selected by extremities in stress-induced self-grooming on the elevated plus maze (EPM), display differences in stress coping style on the EPM, their motivation to self-administer cocaine, and differences in the reactivity of dopaminergic nerve terminals in mesocorticolimbic brain areas. This indicates a link between coping with a stressful/anxiogenic situation and drug intake. Here, we aimed to determine the molecular correlates of these differences by analyzing the reactivity of the mesocorticolimbic brain areas (the medial prefrontal cortex (mPFC) nucleus accumbens shell (NAS) and ventral tegmental area (VTA)) of HG and LG rats in response to EPM exposure.