1. |
- Apergis-Schoute, John, et al.
(author)
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Editorial : Neuronal Co-transmission
- 2019
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In: Frontiers in Neural Circuits. - : FRONTIERS MEDIA SA. - 1662-5110. ; 13
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Journal article (other academic/artistic)
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2. |
- Bekkouche, Bo M.B., et al.
(author)
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Modeling Nonlinear Dendritic Processing of Facilitation in a Dragonfly Target-Tracking Neuron
- 2021
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 15
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Journal article (peer-reviewed)abstract
- Dragonflies are highly skilled and successful aerial predators that are even capable of selectively attending to one target within a swarm. Detection and tracking of prey is likely to be driven by small target motion detector (STMD) neurons identified from several insect groups. Prior work has shown that dragonfly STMD responses are facilitated by targets moving on a continuous path, enhancing the response gain at the present and predicted future location of targets. In this study, we combined detailed morphological data with computational modeling to test whether a combination of dendritic morphology and nonlinear properties of NMDA receptors could explain these observations. We developed a hybrid computational model of neurons within the dragonfly optic lobe, which integrates numerical and morphological components. The model was able to generate potent facilitation for targets moving on continuous trajectories, including a localized spotlight of maximal sensitivity close to the last seen target location, as also measured during in vivo recordings. The model did not, however, include a mechanism capable of producing a traveling or spreading wave of facilitation. Our data support a strong role for the high dendritic density seen in the dragonfly neuron in enhancing non-linear facilitation. An alternative model based on the morphology of an unrelated type of motion processing neuron from a dipteran fly required more than three times higher synaptic gain in order to elicit similar levels of facilitation, despite having only 20% fewer synapses. Our data support a potential role for NMDA receptors in target tracking and also demonstrate the feasibility of combining biologically plausible dendritic computations with more abstract computational models for basic processing as used in earlier studies.
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4. |
- Berthet, Pierre, et al.
(author)
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Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity
- 2016
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In: Frontiers in Neural Circuits. - : FRONTIERS MEDIA SA. - 1662-5110. ; 10
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Journal article (peer-reviewed)abstract
- The brain enables animals to behaviorally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviors are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG) that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1) and the indirect (denoted D2) pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE), which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and post-synaptic activity, receptor type, and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson's disease (PD) by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1.
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5. |
- Björefeldt, Andreas, 1982, et al.
(author)
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Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro Studies.
- 2018
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In: Frontiers in neural circuits. - : Frontiers Media SA. - 1662-5110. ; 12
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Journal article (peer-reviewed)abstract
- The cerebrospinal fluid (CSF) occupies the brain's ventricles and subarachnoid space and, together with the interstitial fluid (ISF), forms a continuous fluidic network that bathes all cells of the central nervous system (CNS). As such, the CSF is well positioned to actively distribute neuromodulators to neural circuitsin vivovia volume transmission. Recentin vitroexperimental work in brain slices and neuronal cultures has shown that human CSF indeed contains neuromodulators that strongly influence neuronal activity. Here we briefly summarize these new findings and discuss their potential relevance to neural circuits in health and disease.
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6. |
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7. |
- Dematties, Dario, et al.
(author)
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A Computational Theory for the Emergence of Grammatical Categories in Cortical Dynamics
- 2020
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In: Frontiers in Neural Circuits. - : FRONTIERS MEDIA SA. - 1662-5110. ; 14
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Journal article (peer-reviewed)abstract
- A general agreement in psycholinguistics claims that syntax and meaning are unified precisely and very quickly during online sentence processing. Although several theories have advanced arguments regarding the neurocomputational bases of this phenomenon, we argue that these theories could potentially benefit by including neurophysiological data concerning cortical dynamics constraints in brain tissue. In addition, some theories promote the integration of complex optimization methods in neural tissue. In this paper we attempt to fill these gaps introducing a computational model inspired in the dynamics of cortical tissue. In our modeling approach, proximal afferent dendrites produce stochastic cellular activations, while distal dendritic branches-on the other hand-contribute independently to somatic depolarization by means of dendritic spikes, and finally, prediction failures produce massive firing events preventing formation of sparse distributed representations. The model presented in this paper combines semantic and coarse-grained syntactic constraints for each word in a sentence context until grammatically related word function discrimination emerges spontaneously by the sole correlation of lexical information from different sources without applying complex optimization methods. By means of support vector machine techniques, we show that the sparse activation features returned by our approach are well suited-bootstrapping from the features returned by Word Embedding mechanisms-to accomplish grammatical function classification of individual words in a sentence. In this way we develop a biologically guided computational explanation for linguistically relevant unification processes in cortex which connects psycholinguistics to neurobiological accounts of language. We also claim that the computational hypotheses established in this research could foster future work on biologically-inspired learning algorithms for natural language processing applications.
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10. |
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11. |
- Geborek, Pontus, et al.
(author)
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Cerebellar cortical neuron responses evoked from the spinal border cell tract.
- 2013
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 7
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Journal article (peer-reviewed)abstract
- Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such as coordination. However, in terms of cerebellar functional analyses, these are perhaps among the least explored systems. The aim of the present study is to achieve activation of a single component of the spinocerebellar systems and to explore to what extent it can influence the spike output of granule cells, Golgi cells, molecular layer (ML) interneurons (stellate and basket cells) and Purkinje cells (PCs). For this purpose, we took advantage of a unique arrangement discovered in neuroanatomical studies, in which the spinal border cell (SBC) component of the ventral spinocerebellar system was found to be the only spinocerebellar tract which ascends in the contralateral lateral funiculus (coLF) and have terminations in sublobulus C1 of the paramedian lobule in the posterior cerebellum. Using electrical stimulation of this tract, we find a subset of the cerebellar cortical neurons in this region to be moderately or powerfully activated. For example, some of our granule cells displayed high intensity responses whereas the majority of the granule cells displayed no response at all. The finding that more than half of the PCs were activated by stimulation of the SBC tract indicated that this system is capable of directly influencing cerebellar cortical output. The implications of these findings for the view of the integrative functions of the cerebellar cortex are discussed.
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12. |
- Geborek, Pontus, et al.
(author)
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Properties of bilateral spinocerebellar activation of cerebellar cortical neurons.
- 2014
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 8
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Journal article (peer-reviewed)abstract
- We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.
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13. |
- Geborek, Pontus, et al.
(author)
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Stimulation within the cuneate nucleus suppresses synaptic activation of climbing fibers.
- 2013
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 6:120, s. 1-9
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Journal article (peer-reviewed)abstract
- Several lines of research have shown that the excitability of the inferior olive is suppressed during different phases of movement. A number of different structures like the cerebral cortex, the red nucleus, and the cerebellum have been suggested as candidate structures for mediating this gating. The inhibition of the responses of the inferior olivary neurons from the red nucleus has been studied extensively and anatomical studies have found specific areas within the cuneate nucleus to be target areas for projections from the magnocellular red nucleus. In addition, GABA-ergic cells projecting from the cuneate nucleus to the inferior olive have been found. We therefore tested if direct stimulation of the cuneate nucleus had inhibitory effects on a climbing fiber field response, evoked by electrical stimulation of the pyramidal tract, recorded on the surface of the cerebellum. When the pyramidal tract stimulation was preceded by weak electrical stimulation (5-20 μA) within the cuneate nucleus, the amplitude of the climbing fiber field potential was strongly suppressed (approx. 90% reduction). The time course of this suppression was similar to that found after red nucleus stimulation, with a peak suppression occurring at 70 ms after the cuneate stimulation. Application of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, disodium salt) on the cuneate nucleus blocked the suppression almost completely. We conclude that a relay through the cuneate nucleus is a possible pathway for movement-related suppression of climbing fiber excitability.
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14. |
- Granseth, Björn, 1973-, et al.
(author)
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Regulation of thalamocortical axon branching by BDNF and synaptic vesicle cycling
- 2013
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 7:202
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Journal article (peer-reviewed)abstract
- During development, axons form branches in response to extracellular molecules. Little is known about the underlying molecular mechanisms. Here, we investigate how neurotrophin-induced axon branching is related to synaptic vesicle cycling for thalamocortical axons. The exogenous application of brain-derived neurotrophic factor (BDNF) markedly increased axon branching in thalamocortical co-cultures, while removal of endogenous BDNF reduced branching. Over-expression of a C-terminal fragment of AP180 that inhibits clathrin-mediated endocytosis affected the laminar distribution and the number of branch points. A dominant-negative synaptotagmin mutant that selectively targets synaptic vesicle cycling, strongly suppressed axon branching. Moreover, axons expressing the mutant synaptotagmin were resistant to the branch-promoting effect of BDNF. These results suggest that synaptic vesicle cycling might regulate BDNF induced branching during the development of the axonal arbor.
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15. |
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16. |
- Hilscher, Markus M., et al.
(author)
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Synchronization through nonreciprocal connections in a hybrid hippocampus microcircuit
- 2013
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 7, s. 120-
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Journal article (peer-reviewed)abstract
- Synchronization among neurons is thought to arise from the interplay between excitation and inhibition; however, the connectivity rules that contribute to synchronization are still unknown. We studied these issues in hippocampal CA1 microcircuits using paired patch clamp recordings and real time computing. By virtually connecting a model interneuron with two pyramidal cells (PCs), we were able to test the importance of connectivity in synchronizing pyramidal cell activity. Our results show that a circuit with a nonreciprocal connection between pyramidal cells and no feedback from PCs to the virtual interneuron produced the greatest level of synchronization and mutual information between PC spiking activity. Moreover, we investigated the role of intrinsic membrane properties contributing to synchronization where the application of a specific ion channel blocker, ZD7288 dramatically impaired PC synchronization. Additionally, background synaptic activity, in particular arising from NMDA receptors, has a large impact on the synchrony observed in the aforementioned circuit. Our results give new insights to the basic connection paradigms of microcircuits that lead to coordination and the formation of assemblies.
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17. |
- Hokfelt, Tomas, et al.
(author)
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Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness
- 2018
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In: Frontiers in Neural Circuits. - : FRONTIERS MEDIA SA. - 1662-5110. ; 12
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Research review (peer-reviewed)abstract
- Neuropeptides are auxiliary messenger molecules that always co-exist in nerve cells with one or more small molecule (classic) neurotransmitters. Neuropeptides act both as transmitters and trophic factors, and play a role particularly when the nervous system is challenged, as by injury, pain or stress. Here neuropeptides and coexistence in mammals are reviewed, but with special focus on the 29/30 amino acid galanin and its three receptors GalR1, -R2 and -R3. In particular, galanins role as a co-transmitter in both rodent and human noradrenergic locus coeruleus (LC) neurons is addressed. Extensive experimental animal data strongly suggest a role for the galanin system in depression-like behavior. The translational potential of these results was tested by studying the galanin system in postmortem human brains, first in normal brains, and then in a comparison of five regions of brains obtained from depressed people who committed suicide, and from matched controls. The distribution of galanin and the four galanin system transcripts in the normal human brain was determined, and selective and parallel changes in levels of transcripts and DNA methylation for galanin and its three receptors were assessed in depressed patients who committed suicide: upregulation of transcripts, e.g., for galanin and GalR3 in LC, paralleled by a decrease in DNA methylation, suggesting involvement of epigenetic mechanisms. It is hypothesized that, when exposed to severe stress, the noradrenergic LC neurons fire in bursts and release galanin from their soma/dendrites. Galanin then acts on somato-dendritic, inhibitory galanin autoreceptors, opening potassium channels and inhibiting firing. The purpose of these autoreceptors is to act as a brake to prevent overexcitation, a brake that is also part of resilience to stress that protects against depression. Depression then arises when the inhibition is too strong and long lasting - a maladaption, allostatic load, leading to depletion of NA levels in the forebrain. It is suggested that disinhibition by a galanin antagonist may have antidepressant activity by restoring forebrain NA levels. A role of galanin in depression is also supported by a recent candidate gene study, showing that variants in genes for galanin and its three receptors confer increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events. In summary, galanin, a neuropeptide coexisting in LC neurons, may participate in the mechanism underlying resilience against a serious and common disorder, MDD. Existing and further results may lead to an increased understanding of how this illness develops, which in turn could provide a basis for its treatment.
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19. |
- Jörntell, Henrik, et al.
(author)
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Receptive Field Remodeling Induced by Skin Stimulation in Cerebellar Neurons in vivo.
- 2011
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 5
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Journal article (peer-reviewed)abstract
- The receptive field of a neuron reflects its function. For example, for parallel fiber (PF) inputs in C3 zone the cerebellar cortex, the excitatory and inhibitory receptive fields of a Purkinje cell (PC) have different locations, and each location has a specific relationship to the location of the climbing fiber (CF) receptive field of the PC. Previous studies have shown that this pattern of input connectivity to the PC and its afferent inhibitory interneurons can be fundamentally disrupted by applying direct electrical stimulation to the PFs, paired or unpaired with CF activation, with protocols that induce plasticity in these synapses. However, afferent fiber stimulation, which is typically used in experimental studies of plasticity, set up highly artificial input patterns at the level of the recipient cells, raising the issue that these forms of plasticity potentially may not occur under more natural input patterns. Here we used skin stimulation to set up spatiotemporally more realistic afferent input patterns in the PFs to investigate whether these input patterns are also capable of inducing synaptic plasticity using similar protocols that have previously been described for direct PF stimulation. We find that receptive field components can be added to and removed from PCs and interneurons following brief periods of skin stimulation. Following these protocols, the receptive fields of mossy fibers were unchanged. These findings confirm that previously described plasticity protocols may have a functional role also for more normal patterns of afferent input.
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20. |
- Kaplan, Bernhard A., et al.
(author)
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A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system
- 2014
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 8, s. 5-
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Journal article (peer-reviewed)abstract
- Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin-Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian-Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian-Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures.
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21. |
- Krishnamurthy, Pradeep, et al.
(author)
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Long-range recruitment of Martinotti cells causes surround suppression and promotes saliency in an attractor network model
- 2015
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 9
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Journal article (peer-reviewed)abstract
- Although the importance of long-range connections for cortical information processing has been acknowledged for a long time, most studies focused on the long-range interactions between excitatory cortical neurons. Inhibitory interneurons play an important role in cortical computation and have thus far been studied mainly with respect to their local synaptic interactions within the cortical microcircuitry. A recent study showed that long-range excitatory connections onto Martinotti cells (MC) mediate surround suppression. Here we have extended our previously reported attractor network of pyramidal cells (PC) and MC by introducing long-range connections targeting MC. We have demonstrated how the network with Martinotti cell-mediated long-range inhibition gives rise to surround suppression and also promotes saliency of locations at which simple non-uniformities in the stimulus field are introduced. Furthermore, our analysis suggests that the presynaptic dynamics of MC is only ancillary to its orientation tuning property in enabling the network with saliency detection. Lastly, we have also implemented a disinhibitory pathway mediated by another interneuron type (VIP interneurons), which inhibits MC and abolishes surround suppression.
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22. |
- Lindroos, Robert, et al.
(author)
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Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales-Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2
- 2018
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In: Frontiers in Neural Circuits. - : Frontiers Media S.A.. - 1662-5110. ; 12
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Journal article (peer-reviewed)abstract
- The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level dopaminergic effects. In particular we predict dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical aspects of the onset of neuromodulation effects in multi-scale computational models combining biochemical signaling cascades and multi-compartmental neuron models.
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23. |
- Matynia, Anna, et al.
(author)
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Peripheral sensory neurons expressing melanopsin respond to light
- 2016
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 10:AUG
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Journal article (peer-reviewed)abstract
- The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.
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24. |
- Mogensen, Hannes, et al.
(author)
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Absence of repetetive correlation patterns between pairs of adjacent neocortical neurons in vivo
- 2019
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In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 13
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Journal article (peer-reviewed)abstract
- Neuroanatomy suggests that adjacent neocortical neurons share a similar set of afferent synaptic inputs, as opposed to neurons localized to different areas of the neocortex. In the present study, we made simultaneous single-electrode patch clamp recordings from two or three adjacent neurons in the primary somatosensory cortex (S1) of the ketamine-xylazine anesthetized rat in vivo to study the correlation patterns in their spike firing during both spontaneous and sensory-evoked activity. One difference with previous studies of pairwise neuronal spike firing correlations was that here we identified several different quantifiable parameters in the correlation patterns by which different pairs could be compared. The questions asked were if the correlation patterns between adjacent pairs were similar and if there was a relationship between the degree of similarity and the layer location of the pairs. In contrast, our results show that for putative pyramidal neurons within layer III and within layer V, each pair of neurons is to some extent unique in terms of their spiking correlation patterns. Interestingly, our results also indicated that these correlation patterns did not substantially alter between spontaneous and evoked activity. Our findings are compatible with the view that the synaptic input connectivity to each neocortical neuron is at least in some aspects unique. A possible interpretation is that plasticity mechanisms, which could either be initiating or be supported by transcriptomic differences, tend to differentiate rather than harmonize the synaptic weight distributions between adjacent neurons of the same type.
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25. |
- Nersisyan, Syune, et al.
(author)
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Cholinergic and Noradrenergic Modulation of Corticothalamic Synaptic Input From Layer 6 to the Posteromedial Thalamic Nucleus in the Rat
- 2021
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In: Frontiers in Neural Circuits. - : Frontiers Media S.A.. - 1662-5110. ; 15
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Journal article (peer-reviewed)abstract
- Cholinergic and noradrenergic neuromodulation of the synaptic transmission from cortical layer 6 of the primary somatosensory cortex to neurons in the posteromedial thalamic nucleus (PoM) was studied using an in vitro slice preparation from young rats. Cholinergic agonist carbachol substantially decreased the amplitudes of consecutive excitatory postsynaptic potentials (EPSPs) evoked by a 20 Hz five pulse train. The decreased amplitude effect was counteracted by a parallel increase of synaptic frequency-dependent facilitation. We found this modulation to be mediated by muscarinic acetylcholine receptors. In the presence of carbachol the amplitudes of the postsynaptic potentials showed a higher trial-to-trial coefficient of variation (CV), which suggested a presynaptic site of action for the modulation. To substantiate this finding, we measured the failure rate of the excitatory postsynaptic currents in PoM cells evoked by "pseudominimal" stimulation of corticothalamic input. A higher failure-rate in the presence of carbachol indicated decreased probability of transmitter release at the synapse. Activation of the noradrenergic modulatory system that was mimicked by application of norepinephrine did not affect the amplitude of the first EPSP evoked in the five-pulse train, but later EPSPs were diminished. This indicated a decrease of the synaptic frequency-dependent facilitation. Treatment with noradrenergic alpha-2 agonist clonidine, alpha-1 agonist phenylephrine, or beta-receptor agonist isoproterenol showed that the modulation may partly rely on alpha-2 adrenergic receptors. CV analysis did not suggest a presynaptic action of norepinephrine. We conclude that cholinergic and noradrenergic modulation act as different variable dynamic controls for the corticothalamic mechanism of the frequency-dependent facilitation in PoM.
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