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Biomedical subjects

Markku Penttonen

Publications and source records attributed to Markku Penttonen.

7 recordsLinked to original sources

Diazepam binding inhibitor overexpression in mice causes hydrocephalus, decreases plasticity in excitatory synapses and impairs hippocampus-dependent learning.

Diazepam binding inhibitor (DBI) and its processing products are endogenous modulators of GABAA and linked to various brain disorders ranging from anxiety and drug dependence to epilepsy. To investigate the physiological role of endogenously expressed DBI in the brain we created a transgenic mouse line overexpressing DBI gene. Transgenic mice had a 37x increased protein expression and immunohistochemistry showed excessive glial expression in the infragranular region of the dentate gyrus. Transgenic animals had significantly larger lateral ventricles and decreased plasticity of excitatory synapses without affecting either inhibitory or excitatory synaptic transmission. In behavioral tests transgenic animals had no differences in motor and exploratory activity, yet impaired hippocampus-dependent learning and memory. Overexpression did not cause anxiety or proconflict behavior, nor influenced kainic acid or pentylenetetrazole induced seizure activity. Our transgenic mouse line demonstrates that endogenously overexpressed DBI impairs hippocampus-dependent learning without anxiety or proconflict behavior.

Animals↗

Memory-based detection of rare sound feature combinations in anesthetized rats.

It is unclear whether the ability of the brain to discriminate rare from frequently repeated combinations of sound features is limited to the normal sleep/wake cycle. We recorded epidural auditory event-related potentials in urethane-anesthetized rats presented with rare tones ('deviants') interspersed with frequently repeated ones ('standards'). Deviants differed from standards either in frequency alone or in frequency combined with intensity. In both cases, deviants elicited event-related potentials exceeding in amplitude event-related potentials to standards between 76 and 108 ms from the stimulus onset, suggesting the independence of the underlying integrative and memory-based change detection mechanisms of the brain from the normal sleep/wake cycle. The relations of these event-related potentials to mismatch negativity and N1 in humans are addressed.

Acoustic Stimulation↗

Contribution of a single CA3 neuron to network synchrony.

Oscillations at theta (3-8 Hz) and gamma (30-80 Hz) frequencies co-occur during arousal, exploration, and rapid eye movement sleep and relate to information processing underlying learning and memory within neuronal networks. In hippocampus, gamma and theta frequency oscillations are associated with modification of synaptic weights, spatial learning, and short-term memory. These oscillations are referred to as network phenomena and, thereby, the role of single neuron oscillations in the generation of neuronal networks remains unclear. We report that an individual CA3 pyramidal cell can activate the CA1 neuronal network in vivo in rat hippocampus using electrical stimulations with simultaneous intracellular gamma and extracellular theta and slow (0.5-1 Hz) frequencies. These results suggest that an individual pyramidal cell can contribute to self-organization of a neuronal small-scale network.

Animals↗

Independent component analysis of neural populations from multielectrode field potential measurements.

Independent component analysis (ICA) is proposed for analysis of neural population activity from multichannel electrophysiological field potential measurements. The proposed analysis method provides information on spatial extents of active neural populations, locations of the populations with respect to each other, population evolution, including merging and splitting of populations in time, and on time lag differences between the populations. In some cases, results of the proposed analysis may also be interpreted as independent information flows carried by neurons and neural populations. In this paper, a detailed description of the analysis method is given. The proposed analysis is demonstrated with an illustrative simulation, and with an exemplary analysis of an in vivo multichannel recording from rat hippocampus. The proposed method can be applied in analysis of any recordings of neural networks in which contributions from a number of neural populations or information flows are simultaneously recorded via a number of measurement points, as well in vivo as in vitro.

Algorithms↗

Epileptic seizure detection: a nonlinear viewpoint.

This study concerns the detection of epileptic seizures from electroencephalogram (EEG) data using computational methods. Using short sliding time windows, a set of features is computed from the data. The feature set includes time domain, frequency domain and nonlinear features. Discriminant analysis is used to determine the best seizure-detecting features among them. The findings suggest that the best results can be achieved by using a combination of features from the linear and nonlinear realms alike.

Algorithms↗

Effects of intracellular pH, blood, and tissue oxygen tension on T1rho relaxation in rat brain.

The effects of intracellular pH (pH(i)), paramagnetic macroscopic, and microscopic susceptibility on T(1) in the rotating frame (T(1rho)) were studied in rat brain. Intracellular acidosis was induced by hypercapnia and pH(i), T(1rho), T(2), diffusion, and cerebral blood volume (CBV) were quantified. Taking into account the CBV contribution, a prolongation of parenchymal T(1rho) by 4.5% was ascribed to a change in tissue water relaxation caused by a one unit drop in pH(i). Blood T(1rho) was found to prolong linearly with blood oxygenation saturation (Y). The macroscopic susceptibility contribution to parenchymal T(1rho) was assessed both through BOLD and an iron oxide contrast agent, AMI-227. The T(1rho) data from these experiments could be described by intravascular effects with insignificant effects of susceptibility gradients on tissue water. Tissue oxygen tension (PtO(2)) was manipulated and monitored with microelectrodes to assess its plausible contribution to microscopic susceptibility and relaxation. Parenchymal T(1rho) was virtually unaffected by variations in the PtO(2), but T(1) was shortened in hyperoxia and T(2) showed a negative BOLD effect in hypoxia. It is demonstrated that pH(i) directly modulates tissue T(1rho), possibly through its effect on proton exchange; however, neither BOLD nor PtO(2) directly influence tissue T(1rho). The observations are discussed in the light of physicochemical mechanisms contributing to the ischemic T(1rho) changes.

Animals↗

Quantitative assessment of the balance between oxygen delivery and consumption in the rat brain after transient ischemia with T2 -BOLD magnetic resonance imaging.

The balance between oxygen consumption and delivery in the rat brain after exposure to transient ischemia was quantitatively studied with single-spin echo T2-BOLD (blood oxygenation level-dependent) magnetic resonance imaging at 4.7 T. The rats were exposed to graded common carotid artery occlusions using a modification of the four-vessel model of Pulsinelli. T2, diffusion, and cerebral blood volume were quantified with magnetic resonance imaging, and CBF was measured with the hydrogen clearance method. A transient common carotid artery occlusion below the CBF value of approximately 20 mL x 100 g(-1) x min(-1) was needed to yield a T2 increase of 4.6 +/- 1.2 milliseconds (approximately 9% of cerebral T2) and 6.8 +/- 1.7 milliseconds (approximately 13% of cerebral T2) after 7 and 15 minutes of ischemia, respectively. Increases in CBF of 103 +/- 75% and in cerebral blood volume of 29 +/- 20% were detected in the reperfusion phase. These hemodynamic changes alone could account for only approximately one third of the T2 increase in luxury perfusion, suggesting that a substantial increase in blood oxygen saturation (resulting from reduced oxygen extraction by the brain) is needed to explain the magnetic resonance imaging observation.

Animals↗