| 1. |
- Abrahamsson, Therése, 1976, et al.
(författare)
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AMPA silencing is a prerequisite for developmental long-term potentiation in the hippocampal CA1 region.
- 2008
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598.
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Tidskriftsartikel (refereegranskat)abstract
- AMPA unsilencing is an often proposed expression mechanism both for developmental LTP, involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3-CA1 connection naïve (non-stimulated) synapses are AMPA-signaling, and AMPA-silent synapses are created from naïve AMPA-signaling (AMPA-labile) synapses by test pulse synaptic activation (AMPA silencing). To investigate to what extent LTP at different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naïve synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naïve synaptic strength. Thus, this early, or developmental, LTP is nothing more than an unsilencing (de-depression), and stabilization, of the AMPA signaling that was lost by the prior AMPA silencing. This de-depression and stabilization of AMPA signaling was mimicked by the presence of the PKA-activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a "genuine" potentiation (as opposed to a de-depression) not explained by unsilencing and stabilization of AMPA-labile synapses. This "genuine", or mature, LTP rose from close to nothing of total LTP prior to P13, to about 70 % of total LTP at P16, and to about 90 % of total LTP at P30. Developmental LTP, by stabilization of AMPA labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.
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| 2. |
- Abrahamsson, Therése, 1976, et al.
(författare)
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Reversible synaptic depression in developing rat CA3-CA1 synapses explained by a novel cycle of AMPA silencing-unsilencing
- 2007
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Ingår i: JOURNAL OF NEUROPHYSIOLOGY. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 98:5, s. 2604-2611
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Tidskriftsartikel (refereegranskat)abstract
- In the developing hippocampus, experiments using whole cell recordings have shown that a small number of synaptic activations can convert many glutamate synapses to AMPA silent synapses. This depression of AMPA signaling is induced by low-frequency (0.05–0.2 Hz) activation, does not require N-methyl-d-aspartate or metabotropic glutamate receptor activation for its induction, and does not readily reverse after stimulus interruption. Here we show, using field recordings and perforated patch-clamp recordings of transmission in developing CA3–CA1 synapses, that this synaptic depression also can be observed under more noninvasive recording conditions. Moreover, under these conditions, the synaptic depression spontaneously recovers within 20 min by the absence of synaptic activation alone, with a time constant of ∼7 min as determined by field excitatory postsynaptic potential recordings. Thus as for the expression of long-term potentiation (LTP), recovery from this depression is susceptible to whole cell dialysis (“wash-out”). In contrast to LTP-induced unsilencing, the AMPA signaling after stimulus interruption was again labile, resumed stimulation resulted in renewed depression. The present study has thus identified a novel cycle for AMPA signaling in which the nascent glutamate synapse cycles between an AMPA silent state, induced by a small number of synaptic activations, and a labile AMPA signaling, induced by prolonged inactivity.
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| 3. |
- Ackerley, Rochelle, 1980, et al.
(författare)
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Case Studies in Neuroscience: Sensations elicited and discrimination ability from nerve cuff stimulation in an amputee over time
- 2018
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 120:1, s. 291-295
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Tidskriftsartikel (refereegranskat)abstract
- The present case study details sensations elicited by electrical stimulation of peripheral nerve axons using an implanted nerve cuff electrode, in a participant with a transhumeral amputation. The participant uses an osseointegrated electromechanical interface, which enables skeletal attachment of the prosthesis and long-term, stable, bidirectional communication between the implanted electrodes and prosthetic arm. We focused on evoking somatosensory percepts, where we tracked and quantified the evolution of perceived sensations in the missing hand. which were evoked from electrical stimulation of the nerve, for over 2 yr. These sensations included small, pointlike areas of either vibration or pushing, to larger sensations over wider areas, indicating the recruitment of a few and many afferents, respectively. Furthermore, we used a two-alternative forced choice paradigm to measure the level of discrimination between trains of brief electrical stimuli, to gauge what the participant could reliably distinguish between. At best, the participant was able to distinguish a 05-Hz difference and on average acquired a 3.8-Hz just-noticeable difference at a more stringent psychophysical level. The current work shows the feasibility for long-term sensory feedback in prostheses, via electrical axonal stimulation, where small and relatively stable percepts were felt that may be used to deliver graded sensory feedback. This opens up opportunities for signaling feedback during movements (e.g., for precision grip), but also for conveying more complex cutaneous sensations. such as texture. NEW & NOTEWORTHY We demonstrate the long-term stability and generation of sensations from electrical peripheral nerve stimulation in an amputee. through an osseointegrated implant. We find that perceived tactilelike sensations could be generated for over 2 yr. in the missing hand. This is useful for prosthetic development and the implementation of feedback in artificial body parts.
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| 4. |
- Ackerley, Rochelle, 1980, et al.
(författare)
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Differential effects of radiant and mechanically applied thermal stimuli on human C-tactile afferent firing patterns.
- 2018
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 120:4, s. 1885-1892
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Tidskriftsartikel (refereegranskat)abstract
- C-tactile (CT) afferents respond to gentle tactile stimulation, but only a handful of studies in humans and animals have investigated whether their firing is modified by temperature. We describe the effects of radiant thermal stimuli, and of stationary and very slowly moving mechanothermal stimuli, on CT afferent responses. We find that CT afferents are primarily mechanoreceptors, as they fired little during radiant thermal stimuli, but they exhibited different patterns of firing during combined mechano-cool stimulation compared with warming. CTs fired optimally to gentle, very slowly moving, or stationary mechanothermal stimuli delivered at neutral temperature (~32°C, normal skin temperature), but they responded with fewer spikes (median 67% decrease) and at significantly lower rates (47% decrease) during warm (~42°C) tactile stimuli. During cool tactile stimuli (~18°C), their mean instantaneous firing frequency significantly decreased by 35%, but they often fired a barrage of afterdischarge spikes at a low frequency (~5 Hz) that outlasted the mechanical stimulus. These effects were observed under a variety of stimulus conditions, including during stationary and slowly moving touch (0.1 cm/s), and we complemented these tactile approaches using a combined electrical-thermal stimulation experiment where we found a suppression of spiking during warming. Overall, CT afferents are exquisitely sensitive to tactile events, and we show that their firing is modulated with touch temperatures above and below neutral skin temperature. Warm touch consistently decreased their propensity to fire, whereas cool touch produced lower firing rates but afterdischarge spiking. NEW & NOTEWORTHY C-tactile (CT) afferents are thought to underpin pleasant touch, and previous work has shown that they respond optimally to a slow caress delivered at typical (neutral) skin temperature. Here, we show that, although CTs are primarily mechanoreceptive afferents, they are modified by temperature: warm touch decreases their firing, whereas cool touch produces lower firing rates but long-lasting spiking, frequently seen as afterdischarges. This has implications for the encoding of affective sensory events in human skin.
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| 5. |
- Ackerley, Rochelle, 1980, et al.
(författare)
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Microneurography as a tool to study the function of individual C-fiber afferents in humans: responses from nociceptors, thermoreceptors, and mechanoreceptors
- 2018
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 120:6, s. 2834-2846
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Tidskriftsartikel (refereegranskat)abstract
- The technique of microneurography-recording neural traffic from nerves in awake humans-has provided us with unrivaled insights into afferent and efferent processes in the peripheral nervous system for over 50 years. We review the use of microneurography to study single C-fiber afferents and provide an overview of the knowledge gained, with views to future investigations. C-fibers have slowly conducting, thin-diameter, unmyelinated axons and make up the majority of the fibers in peripheral nerves (similar to 80%). With the use of microneurography in humans, C-fiber afferents have been differentiated into discrete subclasses that encode specific qualities of stimuli on the skin, and their functional roles have been investigated. Afferent somatosensory information provided by C-fibers underpins various positive and negative affective sensations from the periphery, including mechanical, thermal, and chemical pain (C-nociceptors), temperature (C-thermoreceptors), and positive affective aspects of touch (C-tactile afferents). Insights from microneurographic investigations have revealed the complexity of the C-fiber system, methods for delineating fundamental C-fiber populations in a translational manner, how C-fiber firing can be used to identify nerve deficits in pathological states, and how the responses from C-fibers may be modified to change sensory percepts, including decreasing pain. Understanding these processes may lead to future medical interventions to diagnose and treat C-fiber dysfunction. NEW & NOTEWORTHY The technique of microneurography allows us to directly investigate the functional roles of single C-fiber afferents in awake human beings. Here we outline and discuss the current field of C-fiber research on this heterogeneous population of afferents in healthy subjects, in pathological states, and from a translational perspective. We cover C-fibers encoding touch, temperature, and pain and provide perspectives on the future of C-fiber microneurography investigations in humans.
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| 6. |
- Agnati, LF, et al.
(författare)
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Functional roles of three cues that provide nonsynaptic modes of communication in the brain: electromagnetic field, oxygen, and carbon dioxide
- 2018
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 119:1, s. 356-368
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Tidskriftsartikel (refereegranskat)abstract
- The integrative actions of the brain depend on the exchange of information among its computational elements. Hence, this phenomenon plays the key role in driving the complex dynamics of the central nervous system, in which true computations interact with noncomputational dynamical processes to generate brain representations of the body and of the body in the external world, and hence the finalistic behavior of the organism. In this context, it should be pointed out that, besides the intercellular interactions mediated by classical electrochemical signals, other types of interactions, namely, “cues” and “coercions,” also appear to be exploited by the system to achieve its function. The present review focuses mainly on cues present in the environment and on those produced by cells of the body, which “pervade” the brain and contribute to its dynamics. These cues can also be metabolic substrates, and, in most cases, they are of fundamental importance to brain function and the survival of the entire organism. Three of these highly pervasive cues will be analyzed in greater detail, namely, oxygen, carbon dioxide, and electromagnetic fields (EMF). Special emphasis will be placed on EMF, since several authors have suggested that these highly pervasive energy fluctuations may play an important role in the global integrative actions of the brain; hence, EMF signaling may transcend classical connectionist models of brain function. Thus the new concept of “broadcasted neuroconnectomics” has been introduced, which transcends the current connectomics view of the brain.
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| 7. |
- Almeida, R, et al.
(författare)
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Neural circuit basis of visuo-spatial working memory precision: a computational and behavioral study
- 2015
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 114:3, s. 1806-1818
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Tidskriftsartikel (refereegranskat)abstract
- The amount of information that can be retained in working memory (WM) is limited. Limitations of WM capacity have been the subject of intense research, especially in trying to specify algorithmic models for WM. Comparatively, neural circuit perspectives have barely been used to test WM limitations in behavioral experiments. Here we used a neuronal microcircuit model for visuo-spatial WM (vsWM) to investigate memory of several items. The model assumes that there is a topographic organization of the circuit responsible for spatial memory retention. This assumption leads to specific predictions, which we tested in behavioral experiments. According to the model, nearby locations should be recalled with a bias, as if the two memory traces showed attraction or repulsion during the delay period depending on distance. Another prediction is that the previously reported loss of memory precision for an increasing number of memory items (memory load) should vanish when the distances between items are controlled for. Both predictions were confirmed experimentally. Taken together, our findings provide support for a topographic neural circuit organization of vsWM, they suggest that interference between similar memories underlies some WM limitations, and they put forward a circuit-based explanation that reconciles previous conflicting results on the dependence of WM precision with load.
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| 8. |
- Alstermark, Bror, et al.
(författare)
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In vivo recordings of bulbospinal excitation in adult mouse forelimb motoneurons.
- 2004
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 92:3, s. 1958-62
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Tidskriftsartikel (refereegranskat)abstract
- Here we report on pyramidal and reticulospinal excitation in forelimb motoneurons in the adult mouse using intracellular recordings in vivo. The results have been obtained in BALB/C mice, which were anesthetized with midazolam fentanyl/fluanison. In contrast to the rat, only weak and infrequent pyramidal excitation could be evoked with a minimal trisynaptic linkage. Disynaptic reticulospinal excitation could always be evoked, as well as monosynaptic excitation from the medial longitudinal fasciculus. The results suggest that the reticulospinal pathway in the mouse is important in voluntary motor control of the forelimbs and that the role of the corticospinal tract might be different in mouse compared with rat. Our study provides an opening for studying the effect of genetic manipulation on specified descending systems in the mouse in vivo.
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| 9. |
- Alstermark, Bror, et al.
(författare)
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Lack of monosynaptic corticomotoneuronal EPSPs in rats : disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons.
- 2004
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 91:4, s. 1832-9
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Tidskriftsartikel (refereegranskat)abstract
- In the rat, some findings have been taken to suggest the existence of monosynaptic corticomotoneuronal (CM) connections. Because this connection is believed to be largely responsible for the ability to make independent digit movements in primates and man, it has been inferred that the monosynaptic CM connection in the rat is likewise important for skilled prehension. Comparison of intra- and extracellular recordings from forelimb motoneurons in anesthetized rats, revealed no monosynaptic CM excitatory postsynaptic potentials (EPSPs). The fastest descending excitation in forelimb motoneurons was disynaptically mediated via a corticoreticulospinal pathway and slowly conducted excitation via corticospinal fibers and segmental interneurons. The findings stress the importance of di- and trisynaptic excitatory corticofugal pathways to forelimb motoneurons in the control of skillful digit movements.
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| 10. |
- Alstermark, Bror, et al.
(författare)
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Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons
- 2011
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 106:1, s. 122-126
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Tidskriftsartikel (refereegranskat)abstract
- In motor control, the general view is still that spinal interneurons mainly contribute to reflexes and automatic movements. The question raised here is whether spinal interneurons can mediate the cortical command for independent finger movements, like a precision grip between the thumb and index finger in the macaque monkey, or if this function depends exclusively on a direct corticomotoneuronal pathway. This study is a followup of a previous report (Sasaki et al. J Neurophysiol 92: 3142-3147, 2004) in which we trained macaque monkeys to pick a small piece of sweet potato from a cylinder by a precision grip between the index finger and thumb. We have now isolated one spinal interneuronal system, the C3-C4 propriospinal interneurons with projection to hand and arm motoneurons. In the previous study, the lateral corticospinal tract (CST) was interrupted in C4/C5 (input intact to the C3-C4 propriospinal interneurons), and in this study, the CST was interrupted in C2 (input abolished). The precision grip could be performed within the first 15 days after a CST lesion in C4/C5 but not in C2. We conclude that C3-C4 propriospinal interneurons also can carry the command for precision grip.
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