Synaptic Information Processing Research Articles

Adaptive Regulation for Noise-Aided Weak Signal Detection inSpiking Neurons

Spiking neurons usually change their membrane properties, especiallyion channel activity, during adaptation or synaptic modification toimprove information processing and transmission. Using simple andbiophysically realistic models, our analyses reveal thatactivity-dependent regulation of membrane properties contributes tosensitivity adaptation that improves the neuron ability of detectingsub-threshold signals in the presence of background noises. Theimprovement is achieved by regulating the conductance of ion channelson the membrane, dependent on the neuron firing activity.

Synaptic information processing by astrocytes

Glial cells were classically considered as supportive cells that do not contribute to information processing in the nervous system. However, considerable amount of evidence obtained by several groups during the last few years has demonstrated the existence of a bidirectional communication between astrocytes and neurons, which prompted a re-examination of the role of glial cells in the physiology of the nervous system. This review will discuss recent advances in the neuron-to-astrocyte communication, focusing on the recently reported properties of the synaptically evoked astrocyte Ca 2+ signal that indicate that astrocytes show integrative properties for synaptic information processing. Indeed, we have recently shown that hippocampal astrocytes discriminate between the activity of different synapses, and respond selectively to different axon pathways. Furthermore, the astrocyte Ca 2+ signal is modulated by the simultaneous activity of different synaptic inputs. This Ca 2+ signal modulation depends on cellular intrinsic properties of the astrocytes, is bidirectionally regulated by the level of synaptic activity, and controls the spatial extension of the intracellular Ca 2+ signal. Consequently, we propose that astrocytes can be considered as cellular elements involved in information processing by the nervous system.

Synaptotrophin, a novel neurotrophin required for synaptic integrity and information processing

Synaptotrophin, a novel neurotrophin required for synaptic integrity and information processing

Dopamine-Mediated Disinhibition in the CA1 Region of Rat Hippocampus via D3 Receptor Activation

The hippocampal formation is thought to contribute to both addictive behaviors and to psychotic disorders, and the actions of the neurotransmitter dopamine are intimately involved with these disease states. We have used both whole-cell and extracellular recording techniques in hippocampal slices to investigate the actions of both cocaine and dopamine receptor agonists in the CA1 region. In the presence of cocaine (10 microM), endogenously released dopamine decreased monosynaptic inhibitory postsynaptic currents (IPSCs) evoked from stratum radiatum but not from stratum oriens. This effect of cocaine was not blocked by the D(1/5) antagonist SCH 23390 ({R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine}) (3 microM), whereas several D(2)-like dopamine receptor antagonists prevented the cocaine-induced decrease in the IPSC. The most selective of the effective antagonists tested was the D(3) antagonist, U 99194 ({5,6-dimethoxy-indan-2-yl dipropylamine}) maleate (1 microM). An exogenously applied D(3)-selective dopamine receptor agonist, PD 128907 ({(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]-benzopyrano-[4,3-b]-1,4-oxazin-9-ol}) (1 microM), also significantly inhibited the IPSC, providing further evidence that the activation of the D(3) subtype of dopamine receptor by endogenously released dopamine can modulate inhibition in the CA1 region. This disinhibitory action on pyramidal cells also increased synaptic excitability following Schaffer collateral stimulation, as demonstrated by either a decrease in paired-pulse inhibition of the population spike response or by an increase in the excitatory component of the mixed synaptic response evoked from stratum radiatum. These actions indicate that the activation of D(3) receptors by endogenously released dopamine, especially under conditions of transporter blockade, may significantly impact the processing of synaptic information through the stratum radiatum layer of the hippocampus.

Properties of Synaptically Evoked Astrocyte Calcium Signal Reveal Synaptic Information Processing by Astrocytes

The synaptic control of the astrocytic intracellular Ca2+ is crucial in the reciprocal astrocyte-neuron communication. Using electrophysiological and Ca2+ imaging techniques in rat hippocampal slices, we investigated the astrocytic Ca2+ signal modulation induced by synaptic terminals that use glutamate and acetylcholine. Ca2+ elevations were evoked by glutamate released from Schaffer collaterals and by acetylcholine, but not glutamate, released by alveus stimulation, indicating that astrocytes discriminate the activity of different synapses belonging to different axon pathways. The Ca2+ signal was modulated bidirectionally by simultaneous activation of both pathways, being depressed at high stimulation frequencies and enhanced at low frequencies. The Ca2+ modulation was attributable to astrocytic intrinsic properties, occurred at discrete regions of the processes, and controlled the intracellular expansion of the Ca2+ signal. In turn, astrocyte Ca2+ signal elicited NMDA receptor-mediated currents in pyramidal neurons. Therefore, because astrocytes discriminate and integrate synaptic information, we propose that they can be considered as cellular elements involved in the information processing by the nervous system.

Glial modulation of synaptic transmission: Insights from the supraoptic nucleus of the hypothalamus.

Astrocytes clear synaptically released glutamate from the extracellular space through high-affinity transporters present on their plasma membrane. By controlling the extracellular level of the main excitatory transmitter in the central nervous system, astrocytes thus contribute prominently to the regulation of overall cellular excitability and synaptic information processing. We recently investigated the influence of the glial environment on glutamatergic and GABAergic neurotransmission in the supraoptic nucleus of the rat hypothalamus under physiological conditions such as lactation that significantly reduce astrocytic coverage of its neurons. By performing electrophysiological analyses on this unique model of dynamic neuronal-glial interactions, we have been able to show that the fine astrocytic processes normally enwrapping synapses serve two important functions. First, they govern the level of activation of presynaptic metabotropic glutamate receptors on glutamatergic terminals, thereby regulating synaptic efficacy at excitatory synapses. Second, they act as a physical and functional barrier to diffusion in the extracellular space, limiting spillover of glutamate and other neuroactive substances and therefore contributing to the regulation of heterosynaptic transmission and intercellular communication.

Potentiation of GABAA Currents after Mechanical Injury of Cortical Neurons

Numerous studies have implicated glutamate receptors, glutamate neurotoxicity, and hyperexcitation in the pathobiology of traumatic brain injury, yet much less is known about the effects of neurotrauma on inhibitory GABA channels of the brain. Using an in vitro cell injury model, we tested whether mild stretch injury altered the GABA(A) currents of cultured rat cortical neurons. The application of 1-100 microM GABA to single pyramidal neurons voltage clamped to -60 mV activated an inward current that reversed near 0 mV in solutions containing symmetrical [Cl-]. This current was inhibited by bicuculline, consistent with mediation by GABA(A) receptor channels. In injured neurons, 50 microM GABA elicited a peak current density of 41.2 +/- 2.6 pA/pF (n = 82), which was significantly larger than in uninjured control neurons, 20.2 +/- 1.7 pA/pF (n = 69, p < 0.01). The GABA(A) currents of injured neurons did not differ from those of control neurons in their sensitivity to GABA or their reversal potentials, suggesting that GABA current potentiation did not result from changes in the agonist affinity or ionic selectivity of the channels. GABA current potentiation was prevented by injuring neurons in the presence of the NMDA antagonist APV, or the CaMKII inhibitor KN93. These results thus suggest that NMDA receptor activation following neuronal injury may potentiate GABA(A) channels through the activation of CaMKII. The increase in GABA(A) receptor function observed following injury could potentially contribute to dysfunctional synaptic function and information processing as well as unconsciousness and coma following human brain trauma.

Synaptic modulation of the interspike interval signatures of bursting pyloric neurons.

The pyloric network of the lobster stomatogastric nervous system is one of the best described assemblies of oscillatory neurons producing bursts of action potentials. While the temporal patterns of bursts have been investigated in detail, those of spikes have received less attention. Here we analyze the intraburst firing patterns of pyloric neurons and the synaptic interactions shaping their dynamics in millisecond time scales not performed before. We find that different pyloric neurons express characteristic, cell-specific firing patterns in their bursts. Nonlinear analysis of the interspike intervals (ISIs) reveals distinctive temporal structures ('interspike interval signatures'), which are found to depend on the synaptic connectivity of the network. We compare ISI patterns of the pyloric dilator (PD), lateral pyloric (LP), and ventricular dilator (VD) neurons in 1) normal conditions, 2) after blocking glutamatergic synaptic connections, and 3) in various functional configurations of the three neurons. Manipulation of the synaptic connectivity results in characteristic changes in the ISI signatures of the postsynaptic neurons. The intraburst firing pattern of the PD neuron is regularized by the inhibitory synaptic connection from the LP neuron as revealed in current-clamp experiments and also as reconstructed with a dynamic clamp. On the other hand, mutual inhibition between the LP and VD neurons tend to produce more irregular bursts with increased spike jitter. The results show that synaptic interactions fine-tune the output of pyloric neurons. The present data also suggest a way of processing of synaptic information: bursting neurons are capable of encoding incoming signals by altering the fine structure of their intraburst spike patterns.

Death by glia

No longer underestimated as only passive and supportive cells in the nervous system, glia have been shown to actively participate in synaptic transmission and information processing. Now, a collection of European researchers have highlighted some pathologic consequences of such signaling between astrocytes, microglia and neurons. Chemokines acting at CXCR4 receptors on astrocytes causes them to release tumor necrosis factor-α (TNFα); TNFα on these astrocytes triggers the formation of prostaglandins, which signals the astrocytes to release glutamate in a calcium-dependent manner. Reactive microglia potentiate this pathway and cause neuronal cell death by releasing two factors: (1) more TNFα, which akes astrocytes release higher — and potentially toxic – levels of glutamate and (2) the HIV coat protein gp120, which interacts with CXCR4 receptors on neurons to induce apoptosis. These complicated and deleterious cellular communications are published in the July issue of Nat. Neurosci.

Mechanosensitive Membrane Traffic and an Optimal Strategy for Volume and Surface Area Regulation in CNS Neurons1

Extrapolating from a body of work on isolated neurons, a model is suggested for how central nervous system (CNS) neurons in situ may handle local swelling and shrinking perturbations so as to interfere minimally with the primary role of neurons, synaptic information processing. The strategy used for osmoregulatory membrane adjustments may first come into play during ontogeny, when it could provide membrane tension sensitive membrane trafficking in arborized neurons subjected to morphogenetic forces.

Extracellular signal-regulated kinase, synaptic plasticity, and memory.

The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), has been studied extensively in recent years for its involvement in synaptic plasticity and memory function. Activation of ERK is coupled to stimulation of cell-surface proteins via several different upstream signaling pathways, and contributes to the regulation of diverse cellular processes, ranging from cell excitability to gene expression. We herein review evidence for ERK's role in different forms of synaptic plasticity and different types of learning paradigms, drawing on examples from different systems in molluscs as well as the mammalian brain. The picture that emerges is that ERK activation in response to conditions that give rise to synaptic and behavioral modification contributes to that modification in a multitude of functionally distinct ways. The functional diversity is likely to be achieved by the operation of multiple, parallel ERK cascades that differ with respect to the subcellular compartments in which ERK exerts its effects and the temporal windows during which the effects are manifested. We conclude that our understanding of the mechanisms by which ERK contributes to synaptic plasticity and memory has much to gain by further study of the signaling events up- and downstream of ERK activation and the spatiotemporal characteristics of ERK activation in association with activity-dependent synaptic modification and information processing.

Enhancement of AMPA-Mediated Current after Traumatic Injury in Cortical Neurons

Overactivation of ionotropic glutamate receptors has been implicated in the pathophysiology of traumatic brain injury. Using an in vitro cell injury model, we examined the effects of stretch-induced traumatic injury on the AMPA subtype of ionotropic glutamate receptors in cultured neonatal cortical neurons. Recordings made using the whole-cell patch-clamp technique revealed that a subpopulation of injured neurons exhibited an increased current in response to AMPA. The current-voltage relationship of these injured neurons showed an increased slope conductance but no change in reversal potential compared with uninjured neurons. Additionally, the EC(50) values of uninjured and injured neurons were nearly identical. Thus, current potentiation was not caused by changes in the voltage-dependence, ion selectivity, or apparent agonist affinity of the AMPA channel. AMPA-elicited current could also be fully inhibited by the application of selective AMPA receptor antagonists, thereby excluding the possibility that current potentiation in injured neurons was caused by the activation of other, nondesensitizing receptors. The difference in current densities between control and injured neurons was abolished when AMPA receptor desensitization was inhibited by the coapplication of AMPA and cyclothiazide or by the use of kainate as an agonist, suggesting that mechanical injury alters AMPA receptor desensitization. Reduction of AMPA receptor desensitization after brain injury would be expected to further exacerbate the effects of increased postinjury extracellular glutamate and contribute to trauma-related cell loss and dysfunctional synaptic information processing.

Information Processing with Frequency-Dependent Synaptic Connections

The efficacy of synaptic transmission between two neurons changes as a function of the history of previous activations of the synaptic connection. This history dependence can be characterized by examining the dependence of transmission on the frequency of stimulation. In this framework synaptic plasticity can also be examined in terms of changes in the frequency dependence of transmission and not merely in terms of synaptic strength which constitutes only a linear scaling mechanism. Recent work shows that the frequency dependence of transmission determines the content of information transmitted between neurons and that synaptic modifications can change the content of information transmitted. Multipatch-clamp recordings revealed that the frequency dependence of transmission is potentially unique for each synaptic connection made by a single axon and that the class of pre–postsynaptic neuron determines the class of frequency dependence (activity independent), while the unique activity relationship between any two neurons could determine the precise values of the parameters within a specific class (activity dependent). The content of information transmitted between neurons is also formalized to provide synaptic transfer functions which can be used to determine the role of the synaptic connection within a network of neurons. It is proposed that deriving synaptic transfer functions is crucial in order to understand the link between synaptic transmission and information processing within networks of neurons and to understand the link between synaptic plasticity and learning and memory.

Transmission and processing of synaptic information in single neurones: an introduction.

Acta Physiologica ScandinavicaVolume 157, Issue 3 p. 367-368 Transmission and processing of synaptic information in single neurones: an introduction O. KIEHN, O. KIEHN Section of Neurophysiology, Department of Medical Physiology, The Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, DenmarkSearch for more papers by this authorJ. MIDTGAARD, J. MIDTGAARD Section of Neurophysiology, Department of Medical Physiology, The Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, DenmarkSearch for more papers by this author O. KIEHN, O. KIEHN Section of Neurophysiology, Department of Medical Physiology, The Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, DenmarkSearch for more papers by this authorJ. MIDTGAARD, J. MIDTGAARD Section of Neurophysiology, Department of Medical Physiology, The Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, DenmarkSearch for more papers by this author First published: July 1996 https://doi.org/10.1046/j.1365-201X.1996.27253000.x Ole Kiehn Section of Neurophysiology, Department of Physiology,The Panum Institute, Blegdamsvej 3, 2200 DK-Copenhagen, Denmark This symposium was organized by Henrik Jahnsen, Ole Kiehn and Jens Midtgaard. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume157, Issue3July 1996Pages 367-368 RelatedInformation

Bilateral organization of parallel and serial pathways in the dentate gyrus demonstrated by current-source density analysis in the rat.

1. Membrane currents evoked in the dentate gyrus (DG) by stimulation of afferent pathways from the entorhinal cortex (EC) and contralateral DG were examined by current-source density (CSD) analysis in urethan-anesthetized rats. Stimulation of each afferent pathway evoked membrane currents with distinct spatial and temporal organization in the DG. CSD and anatomic analysis revealed that afferent input from the EC activated the DG bilaterally through parallel and serial pathways. The analysis provided a detailed description of the location, timing, and relative amplitude of evoked monosynaptic and multisynaptic currents in the DG. 2. Orthodromic stimulation of the perforant path (PP) evoked a large ipsilateral excitatory postsynaptic current (iEPSC) at a latency of 2.5-4 ms in the middle and outer stratum moleculare (STM) of the DG, and a population spike that was generated by an excitatory inward current at a latency of 5-9 ms in the stratum granulosum. 3. A variable, low-amplitude ipsilateral inward current followed the population spike at a latency of 13-16 ms in the inner STM, which is the site of synaptic terminals of the associational and commissural pathways arising from neurons in the hilus of the DG. Orthodromic stimulation of the commissural pathway from the hilus of the contralateral DG also evoked an inward current in the inner STM at a latency of 2-6 ms, which was 40-60% of the amplitude of the monosynaptic iEPSC. 4. Orthodromic stimulation of the EC evoked a low-amplitude contralateral excitatory postsynaptic current (cEPSC) at a latency of 3-6 ms in the outer and middle STM of the contralateral DG, which was generated by monosynaptic transmission in the sparse crossed pathway from the EC. In contrast to the variable, low-amplitude inward current in the inner STM that followed the iEPSC, the cEPSC was consistently followed by a large inward current at a latency of 8-14 ms in the inner STM of the contralateral DG. 5. The large inward current in the inner STM of the contralateral DG was abolished by transection of the PP ipsilateral and rostral to the stimulating electrode, but was unaffected by transection of the PP at a similar location in the hemisphere contralateral to the stimulating electrode. These observations suggested that this current was most likely generated by a multisynaptic pathway involving the ipsilateral PP and the commissural pathway arising from the hilus of the DG. 6. In conclusion, efferents from the EC activated the DG bilaterally by parallel and serial pathways. Parallel monosynaptic pathways from the EC activated homologous distal segments of granule cell dendrites bilaterally, by a massive input to the ipsilateral DG and a sparse input to the contralateral DG. Sequential propagation from the EC through a multisynaptic pathway that included the commissural pathway from the hilus of the DG bilaterally activated the proximal segments of granule cell dendrites at longer latencies. The amplitude of the multisynaptic currents generated by serial pathways in the proximal dendrites varied inversely with the amplitudes of the monosynaptic currents evoked by parallel pathways in the distal dendrites. These observations may have implications for synaptic integration, associative properties, and information processing in the DG.

Evidence that 5'-nucleotidase is associated with malleable synapses--an enzyme cytochemical investigation of the olfactory bulb of adult rats.

The adenosine-producing ecto-enzyme 5'-nucleotidase has recently been assigned to malleable axon terminals in both the developing and regenerating adult nervous system, but is otherwise only glia-bound. Using a cytochemical lead method, we now show that 5'-nucleotidase activity is localized predominantly at glomerular and mitral synapses within the main olfactory bulb of normal, adult rats. As these terminals are prone to synaptic turnover even at maturity, the present findings favour the view that this enzyme constitutes a marker molecule for plastic synapses. It is suggested that functions of 5'-nucleotidase in purinergic neuromodulation and cell adhesion are unique to the olfactory bulb, and implied in synaptic arrangements and information processing.

Processing of synaptic information depends on the structure of the dendritic tree.

The consequences of dendritic geometry for the processing of synaptic information was analysed in two types of motion-sensitive neurones in the visual system of the fly. These neurones differ conspicuously in the morphology of their dendrites but receive their input from the same type of local motion-sensitive elements. Intracellular recording and activating selected regions of the dendrite by visual motion showed that, in accordance with cable theory of nerve cells, the way in which postsynaptic signals interact is essentially determined by the structure of the dendritic tree.

Dendritic processing of synaptic information by sensory interneurons

One of the most distinguishing features of nerve cells is the vast morphological diversity of their input regions, that is, their dendrites. These range from bulbous structures, with only small protrusions, to large tree-like arborizations. The diversity of nerve cells is further augmented by a continuously increasing number of types of voltage-dependent conductances in dendrites that might alter the postsynaptic signals in a pronounced way. Moreover, intracellular factors such as Ca 2+ link electrical activity with biochemical processes, and can induce short and long-term changes in responsiveness. This complexity of neurons in general, and the uniqueness of each cell type, sharply contrasts with the comparatively simple and uniform design principle of the integrate-and-fire units of so-called neuronal net models. This raises the question of which particular structural and physiological details of nerve cells really matter for the performance of neuronal circuits. An answer to this basic problem of computational neurobiology might be given only if the task of the neurons and circuits is known. This review illustrates how the problem can be approached particularly well in sensory interneurons. The functional significance of sensory interneurons can often be assessed more easily than that of central nerve cells because of their vicinity to the sensory surface.

Description of a model of the gyroscope for class illustration

Based on a logic of balance mechanisms influencing information processing in tripartite synapses are proposed. It is hypothesized that the number of expressed astrocytic receptors determines balanced and imbalanced synaptic states. Synaptic information processing in mental disorders is underbalanced in depression, overbalanced in mania, and completely unbalanced in schizophrenia. The synaptic pathophysiology of the epileptic syndrome may also be based on comparable imbalances. In addition, this model of synaptic balancing enables a deduction in explaining the therapeutic effect of ECT in therapy resistant depression. Together, the model proposed may represent a contribution to the search for common synaptic mechanisms in normal brains and its various disorders.