1.
Cervenka, Simon, et al.
(författare)
PET Studies of D2-Receptor Binding in Striatal and Extrastriatal Brain Regions : Biochemical Support In Vivo for Separate Dopaminergic Systems in Humans
2010
Ingår i: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 64:6, s. 478-485
Tidskriftsartikel (refereegranskat) abstract
Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [C-11]raclopride and [C-11]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.
2.
3.
Bulovaite, Edita, et al.
(författare)
A brain atlas of synapse protein lifetime across the mouse lifespan
2022
Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 110:24, s. 4057-
Tidskriftsartikel (refereegranskat) abstract
The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.
4.
Dickson, C. T., et al.
(författare)
Properties and role of I-h in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons
2000
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 83:5, s. 2562-2579
Forskningsöversikt (refereegranskat) abstract
Various subsets of brain neurons express a hyperpolarization-activated inward current (I-h) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na+-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I-h because it was resistant to extracellular Ba2+, sensitive to Cs+, completely and selectively abolished by ZD7288, and carried by both Na+ and K+ ions. I-h in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba2+ gradually and completely abolished the subthreshold oscillations, thus directly implicating I-h in their generation. Using experimentally derived biophysical parameters for I-h and the low-threshold persistent Na+ current (I-NaP) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I-NaP and I-h can sustain persistent subthreshold oscillations in SCs. I-NaP and I-h operate in a push-pull fashion where the delay in the activation/deactivation of I-h gives rise to the oscillatory process.
5.
Egorov, A. V., et al.
(författare)
Graded persistent activity in entorhinal cortex neurons
2002
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 420:6912, s. 173-178
Tidskriftsartikel (refereegranskat) abstract
Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time(1,2). Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential(2). Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions(3)-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.
6.
Eriksson, David, et al.
(författare)
Effects of short-term synaptic plasticity in a local microcircuit on cell firing
2003
Ingår i: Neurocomputing. - : Elsevier BV. - 0925-2312 .- 1872-8286. ; 52-54, s. 7-12
Tidskriftsartikel (refereegranskat) abstract
Effects of short-term synaptic plasticity on cell firing properties in a microcircuit formed by a reciprocally connected pyramidal cell and FSN interneuron in layer 2/3 of neocortex were analyzed in a biophysical model. Induction of synaptic depression by backpropagating dendritic action potentials was replicated, as well as the resulting time dependent depression of IPSP amplitudes. Results indicate that the effect of the depression becomes significant above 30 Hz input frequency. The magnitude of the effect depends on the time constant of the dendritic calcium regulating the depression. The frequency range depends on the time constant of the IPSP.
7.
Fransén, Erik, 1962-, et al.
(författare)
A model of cortical associative memory based on a horizontal network of connected columns
1998
Ingår i: Network. - BRISTOL : IOP PUBLISHING. - 0954-898X .- 1361-6536. ; 9:2, s. 235-264
Tidskriftsartikel (refereegranskat) abstract
An attractor network model of cortical associative memory functions has been constructed and simulated. By replacing the single cell as the functional unit by multiple cells in cortical columns connected by long-range fibers, the model is improved in terms of correspondence with cortical connectivity. The connectivity is improved, since the original dense and symmetric connectivity of a standard recurrent network becomes sparse and asymmetric at the cell-to-cell level. Our simulations show that this kind of network, with model neurons of the Hodgkin-Huxley type arranged in columns, can operate as an associative memory in much the same way as previous models having simpler connectivity. The network shows attractor-like behaviour and performs the standard assembly operations despite differences in the dynamics introduced by the more detailed cell model and network structure. Furthermore, the model has become sufficiently detailed to allow evaluation against electrophysiological and anatomical observations. For instance, cell activities comply with experimental findings and reaction times are within biological and psychological ranges. By introducing a scaling model we demonstrate that a network approaching experimentally reported neuron numbers and synaptic distributions also could work like the model studied here.
8.
Fransén, Erik, 1962-
(författare)
A synapse which can switch from inhibitory to excitatory and back
2005
Ingår i: Neurocomputing. - : Elsevier BV. - 0925-2312 .- 1872-8286. ; 65, s. 39-45
Tidskriftsartikel (refereegranskat) abstract
Co-release of transmitters has recently been observed at synapse terminals and can even be a combination such as glutamate and GABA. A second recent experimental finding is a short-term synaptic plasticity, which depends on postsynaptic depolarization releasing a dendritic transmitter, which affects presynaptic release probability. In this work we are investigating the functional consequences for a synapse if it had both co-release and conditioning depression. If initially the GABA component is larger than the glutamate component, the synapse has an inhibitory net effect. However, if the postsynaptic cell is conditioned, the GABA component will be suppressed yielding an excitatory synapse.
9.
Fransén, Erik, 1962-
(författare)
Coexistence of synchronized oscillatory and desynchronized rate activity in cortical networks
2003
Ingår i: Neurocomputing. - : Elsevier BV. - 0925-2312 .- 1872-8286. ; apr-52, s. 763-769
Tidskriftsartikel (refereegranskat) abstract
The basis of MRI and PET experiments is the finding that neuronal cell firing levels are modulated in a task dependent manner. Results from EEG and MEG experiments on the other hand point to the importance of synchrony, e.g. the peak frequency may depend on the difficulty of the task. In most models only one of these activity modes of firing is desirable or possible to produce. In this work we show how a cortical microcircuit can produce either synchronized or desynchronized firing, and how this solves problems of present day rate and synchronization models.
10.
Fransén, Erik, 1962-, et al.
(författare)
Computational modeling of activity dependent velocity changes in peripheral C-fibers
2011
Konferensbidrag (refereegranskat) abstract
Initiation and propagation of action potentials along unmyelinated C-fibers are the first steps of the pain pathway. Propagation velocity and its fiber class-specific activity-dependent slowing (ADS) is intimately linked to fibre excitability. In chronic pain patients, ADS alterations have been suggested to reflect increased excitability, possibly underlying clinical pain. Due to their small diameter, peripheral axons of nociceptors in patients are not accessible for intraaxonal recordings of their ion channel properties. We have therefore constructed a model of a C-fibre to study the relationship between ion channel composition and velocity changes as well as excitability. Ion channels are modeled from data of DRG somata using a Hodgkin-Huxley formalism (Na currents: TTX-sensitive, Nav1.8, Nav1.9, K currents: Kdr, A-type, Kv7.3, non-specific cationic: HCN). Moreover, ion pumps (Na/K-ATPase) and concentrations of intra and extraaxonal sodium and potassium are also included. The geometry and temperature of the fibre represents a section of the superficial branch and the deeper parent and is represented by a multicompartmental structure where each compartment contains passive as well as ion channel and pump elements. Using parameter estimation techniques, we optimized ion channel and pump expression pattern such that basic electrophysiological characteristics of the action potential and its velocity matched the experimental data. Moreover, we have also replicated activity dependent slowing. In ongoing work, we extend optimization to also include recovery cycles. The model will be used to study hypothesis of the relationship between individual ion channel subtypes and axonal excitability related to pain, generating independent information on impact of selective neuronal targets.
