Ivani Brys

Attention, locomotor activity and developmental milestones in rats prenatally exposed to ethanol.

Decline of attentional performance as a function of time engaged on a task and hyperactivity are features shared by children and adults with fetal alcohol syndrome or attentional deficit and hyperactivity disorders.

Systems-level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia.

Disorders affecting the central nervous system have proven particularly hard to treat, and disappointingly few novel therapies have reached the clinics in recent decades. A better understanding of the physiological processes in the brain underlying various symptoms could therefore greatly improve the rate of progress in this field. We here show how systems-level descriptions of different brain states reliably can be obtained through a newly developed method based on large-scale recordings in distributed neural networks encompassing several different brain structures. Using this technology, we characterize the neurophysiological states associated with parkinsonism and levodopa-induced dyskinesia in a rodent model of Parkinsons disease together with pharmacological interventions aimed at reducing dyskinetic symptoms. Our results show that the obtained electrophysiological data add significant information to conventional behavioral evaluations and hereby elucidate the underlying effects of treatments in greater detail. Taken together, these results potentially open up for studies of neurophysiological mechanisms underlying symptoms in a wide range of neurological and psychiatric conditions that until now have been very hard to investigate in animal models of disease.

Spinal cord stimulation improves forelimb use in an alpha-synuclein animal model of Parkinson's disease.

Neuromodulation by spinal cord stimulation has been proposed as a symptomatic treatment for Parkinsons disease. We tested the chronic effects of spinal cord stimulation in a progressive model of Parkinsons based on overexpression of alpha-synuclein in the substantia nigra. Adult Sprague Dawley rats received unilateral injections of adeno-associated virus serotype 6 (AAV6) in the substantia nigra to express alpha-synuclein. Locomotion and forepaw use of the rats were evaluated during the next 10 weeks. Starting on week 6, a group of AAV6-injected rats received spinal cord stimulation once a week. At the end of the experiment, tyrosine hydroxylase and alpha-synuclein immunostaining were performed. Rats with unilateral alpha-synuclein expression showed a significant decrease in the use of the contralateral forepaw, which was mildly but significantly reverted by spinal cord stimulation applied once a week from the 6th to the 10th week after the AAV6 injection. Long-term spinal cord stimulation proved to be effective to suppress or delay motor symptoms in a sustained and progressive model of Parkinsons and might become an alternative, less invasive neuromodulation option to treat this disease.

Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT 1A receptor biased agonists

ABSTRACT Recently, the biased and highly selective 5‐HT1A agonists, NLX‐112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinsons disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico‐basal ganglia‐thalamic circuits following treatment with this novel group of 5‐HT1A agonists or the prototypical agonist, 8‐OH‐DPAT. Dyskinetic symptoms were consistently associated with 80Hz oscillations, which were efficaciously suppressed by all 5‐HT1A agonists and reappeared upon co‐administration of the antagonist, WAY100635. At the same time, the peak‐frequency of fast 130Hz gamma oscillations and their cross‐frequency coupling to low‐frequency delta oscillations were modified to a different extent by each of the 5‐HT1A agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non‐motor symptoms. HIGHLIGHTSSystems‐level neurophysiological states reveal pharmacological profiles.5‐HT1A receptor biased agonists are antidyskinetic and reduce 80Hz oscillations.5‐HT1A receptor biased agonists show differential effects on fast gamma oscillations.

Motor deficits and beta oscillations are dissociable in an alpha-synuclein model of Parkinson's disease

Parkinsons disease (PD) is a neurodegenerative disorder characterised by progressive motor symptoms resulting from chronic loss of dopaminergic neurons in the nigrostriatal pathway. The over expression of the protein alpha‐synuclein in the substantia nigra has been used to induce progressive dopaminergic neuronal loss and to reproduce key histopathological and temporal features of PD in animal models. However, the neurophysiological aspects of the alpha‐synuclein PD model have been poorly characterised. Hereby, we performed chronic in vivo electrophysiological recordings in the corticostriatal circuit of rats injected with viral vector to over express alpha‐synuclein in the right substantia nigra. Our model, previously shown to exhibit mild motor deficits, presented moderate dopaminergic cell loss but did not present prominent local field potential oscillations in the beta frequency range (11–30 Hz), considered a hallmark of PD, during the 9 weeks after onset of alpha‐synuclein over expression. Spinal cord stimulation, a potential PD symptomatic therapy, was applied regularly from sixth to ninth week after alpha‐synuclein over expression onset and had an inhibitory effect on the firing rate of corticostriatal neurons in both control and alpha‐synuclein hemispheres. Dopamine synthesis inhibition at the end of the experiment resulted in severe parkinsonian symptoms such as akinesia and increased beta and high‐frequency (>90 Hz) oscillations. These results suggest that the alpha‐synuclein PD model with moderate level of dopaminergic depletion does not reproduce the prominent corticostriatal beta oscillatory activity associated to parkinsonian conditions.

Parenthood in the context of maternal depression at the end of the infant's first year of life

The present study investigated parenthood in the context of maternal depression, at the end of the first year of the infants life. The participants of the study were 22 families, from different socioeconomic levels, divided into two groups, one with mothers who did not present indicators of depression (n=12) and another group with mothers who did (n=10), based on the Beck Depression Inventory. All the mothers were primiparous and lived with the childs father, the babies were approximately 12 months of age. The mothers and fathers participated in an interview that investigated several parenting aspects. Qualitative content analysis of the interviews indicated that, compared to the group without depression, the depressed mothers, as well as their husbands, reported more difficulties regarding division tasks, financial concerns, and divergences and conflicts in child care. These results corroborate other studies which emphasized that the presence of indicators of maternal depression can cause difficulties in parenting.

Changes in neuronal activity of cortico-basal ganglia-thalamic networks induced by acute dopaminergic manipulations in rats

The basal ganglia are thought to be particularly sensitive to changes in dopaminergic tone, and the realization that reduced dopaminergic signaling causes pronounced motor dysfunction is the rationale behind dopamine replacement therapy in Parkinsons disease. It has, however, proven difficult to identify which neurophysiological changes that ultimately lead to motor dysfunctions. To clarify this, we have here recorded neuronal activity throughout the cortico‐basal ganglia–thalamic circuits in freely behaving rats during periods of immobility following acute dopaminergic manipulations, involving both vesicular dopamine depletion and antagonism of D1 and D2 type dopamine receptors. Synchronized and rhythmic activities were detected in the form of betaband oscillations in local field potentials and as cortical entrainment of action potentials in several basal ganglia structures. Analyses of the temporal development of synchronized oscillations revealed a spread from cortex to gradually also include deeper structures. In addition, firing rate changes involving neurons in all parts of the network were observed. These changes were typically relatively balanced within each structure, resulting in negligible net rate changes. Animals treated with D1 receptor antagonist showed a rapid onset of hypokinesia that preceded most of the neurophysiological changes, with the exception of these balanced rate changes. Parallel rate changes in functionally coupled ensembles of neurons in different structures may therefore be the first step in a cascade of neurophysiological changes underlying motor symptoms in the parkinsonian state. We suggest that balanced rate changes in distributed networks are possible mechanism of disease that should be further investigated in conditions involving dopaminergic dysfunction.