Pre & postsynaptic tuning of action potential timing by spontaneous GABAergic activity

Frequency and timing of action potential discharge are key elements for coding and transfer of information between neurons. The nature and location of the synaptic contacts, the biophysical parameters of the receptor-operated channels and their kinetics of activation are major determinants of the firing behaviour of each individual neuron. Ultimately the intrinsic excitability of each neuron determines the input-output function. Here we evaluate the influence of spontaneous GABAergic synaptic activity on the timing of action potentials in Layer 2/3 pyramidal neurones in acute brain slices from the somatosensory cortex of young rats. Somatic dynamic current injection to mimic synaptic input events was employed, together with a simple computational model that reproduce subthreshold membrane properties. Besides the well-documented control of neuronal excitability, spontaneous background GABAergic activity has a major detrimental effect on spike timing. In fact, GABA(A) receptors tune the relationship between the excitability and fidelity of pyramidal neurons via a postsynaptic (the reversal potential for GABA(A) activity) and a presynaptic (the frequency of spontaneous activity) mechanism. GABAergic activity can decrease or increase the excitability of pyramidal neurones, depending on the difference between the reversal potential for GABA(A) receptors and the threshold for action potential. In contrast, spike time jitter can only be increased proportionally to the difference between these two membrane potentials. Changes in excitability by background GABAergic activity can therefore only be associated with deterioration of the reliability of spike timing.     

GANGLTOSIDES AND THE ARCHITECTURE OF HUMAN FRONTAL AND RAT SOMATOSENSORY ISOCORTEX

Ganglioside sialic acid was determined in the layers of human frontal association cortex and rat somatosensory cortex by microchemical methods of sampling and analysis. In both cortices the distribution per unit dry weight showed three main peaks or inflections: (1) at the junction of layers II and III; (2) in the lower part of layer III at the junction with IV; and (3) at the junction of layers V and VI. These distributions parallel the occurrence of high concentrations of dendritic and axonal plexuses and their synaptic articulations. In human cortex, the concentration of ganglioside sialic acid per unit dry weight was slightly greater, the amount per cell was twice as great. and the amount per neuron present was 2- to 6-fold greater than in rat somatosensory cortex. The ganglioside sialic acid per cell was 120- to 200-fold greater in human association cortex than in rat retina, which is a CNS region with sparse neuropil. The results support the validity of ganglioside sialic acid as an index of the relative mass of neuronal plasma membranes in neural tissues and its usefulness in chemoanatomic quantitation of axodendritic interrelationships established by synaptic contacts with local and distant neurons.     

Non-associative Potentiation of Perisomatic Inhibition Alters the Temporal Coding of Neocortical Layer 5 Pyramidal Neurons

In the neocortex, the coexistence of temporally locked excitation and inhibition governs complex network activity underlying cognitive functions, and is believed to be altered in several brain diseases. Here we show that this equilibrium can be unlocked by increased activity of layer 5 pyramidal neurons of the mouse neocortex. Somatic depolarization or short bursts of action potentials of layer 5 pyramidal neurons induced a selective long-term potentiation of GABAergic synapses (LTPi) without affecting glutamatergic inputs. Remarkably, LTPi was selective for perisomatic inhibition from parvalbumin basket cells, leaving dendritic inhibition intact. It relied on retrograde signaling of nitric oxide, which persistently altered presynaptic GABA release and diffused to inhibitory synapses impinging on adjacent pyramidal neurons. LTPi reduced the time window of synaptic summation and increased the temporal precision of spike generation. Thus, increases in single cortical pyramidal neuron activity can induce an interneuron-selective GABAergic plasticity effectively altering the computation of temporally coded information.     

Predicting spike timing of neocortical pyramidal neurons by simple threshold models

Neurons generate spikes reliably with millisecond precision if driven by a fluctuating current—is it then possible to predict the spike timing knowing the input? We determined parameters of an adapting threshold model using data recorded in vitro from 24 layer 5 pyramidal neurons from rat somatosensory cortex, stimulated intracellularly by a fluctuating current simulating synaptic bombardment in vivo. The model generates output spikes whenever the membrane voltage (a filtered version of the input current) reaches a dynamic threshold. We find that for input currents with large fluctuation amplitude, up to 75% of the spike times can be predicted with a precision of ±2 ms. Some of the intrinsic neuronal unreliability can be accounted for by a noisy threshold mechanism. Our results suggest that, under random current injection into the soma, (i) neuronal behavior in the subthreshold regime can be well approximated by a simple linear filter; and (ii) most of the nonlinearities are captured by a simple threshold process.     

Paternal deprivation induces dendritic and synaptic changes and hemispheric asymmetry of pyramidal neurons in the somatosensory cortex

Similar to maternal care, paternal care is a source of neonatal sensory stimulation, which in primates and rodents has been shown to be essential for developing structure and function of sensory cortices. The aim of our study in the biparental rodent Octodon degus was to assess the impact of paternal deprivation on dendritic and synaptic development in the somatosensory cortex. We (i) quantified the amount of paternal care in relation to total parental investment and (ii) compared dendritic and synaptic development of pyramidal neurons in the somatosensory cortex of animals raised by a single mother or by both parents. On the behavioral level we show that paternal care comprises 37% of total parent‐offspring interactions, and that the somatosensory stimulation provided by the fathers primarily consists of huddling, licking/grooming, and playing. On the morphological level we found that, compared with offspring raised by both parents (mother and father), the father‐deprived animals displayed significantly reduced spine numbers on the basal dendrites of pyramidal neurons. Furthermore, paternal deprivation induces hemispheric asymmetry of the dendritic morphology of somatosensory pyramidal neurons. Father‐deprived animals show shorter and less complex basal dendrites in the left somatosensory cortex compared with the right hemisphere. These findings indicate that paternal deprivation results in delayed or retarded dendritic and synaptic development of somatosensory circuits. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Structure-Dependent Electrical and Concentration Processes in the Dendrites of Pyramidal Neurons of Superficial Neocortical Layers: Model Study

On mathematical models of pyramidal neurons localized in the neocortical layers 2/3, whose reconstructed dendritic arborization possessed passive linear or active nonlinear membrane properties, we studied the effect of morphology of the dendrites on their passive electrical transfer characteristics and also on the formation of patterns of spike discharges at the output of the cell under conditions of tonic activation via uniformly distributed excitatory synapses along the dendrites. For this purpose, we calculated morphometric characteristics of the size, complexity, metric asymmetry, and function of effectiveness of somatopetal transmission of the current (with estimation of the sensitivity of this efficacy to changes in the uniform membrane conductance) for the reconstructed dendritic arborization in general and also for its apical and basal subtrees. Spatial maps of the membrane potential and intracellular calcium concentration, which corresponded to certain temporal patterns of spike discharges generated by the neuron upon different intensities of synaptic activation, were superimposed on the 3D image and dendrograms of the neuron. These maps were considered “spatial autographs” of the above patterns. The main discharge pattern included periodic two-spike bursts (dublets) generated with relatively stable intraburst interspike intervals and interburst intervals decreasing with a rise in the intensity of activation. Under conditions of intense activation, the interburst intervals became close to the intraburst intervals, so the cell began to generate continuous trains of action potentials. Such a repertoire (consisting of two patterns of the activity, periodical dublets and continuous discharges) is considerably scantier than that described earlier in pyramidal neurons of the neocortical layer 5. Under analogous conditions of activation, we observed in the latter cells a variety of patterns of output discharges of different complexities, including stochastic ones. A relatively short length of the apical dendrite subtree of layer 2/3 neurons and, correspondingly, a smaller metric asymmetry (differences between the lengths of the apical and basal dendritic branches and paths), as compared with those in layer 5 pyramidal neurons, are morphological factors responsible for the predominance of periodic spike dublets. As a result, there were two combinations of different electrical states of the sites of dendritic arborization (“spatial autographs”). In the case of dublets, these were high depolarization of the apical dendrites vs. low depolarization of the basal dendrites and a reverse combination; only the latter (reverse) combination corresponded to the case of continuous discharges. The relative simplicity and uniformity of spike patterns in the cells, apparently, promotes the predominance of network interaction in the processes of formation of the activity of pyramidal neurons of layers 2/3 and, thereby, a higher efficiency of the processes of intracortical association.     

Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5

Neurotrophins are candidate molecules for regulating dendritogenesis. We report here on dendritic growth of rat visual cortex pyramidal and interneurons overexpressing 'brain-derived neurotrophic factor' BDNF and 'neurotrophin 4/5' NT4/5. Neurons in organotypic cultures were transfected with plasmids encoding either 'enhanced green fluorescent protein' EGFP, BDNF/EGFP or NT4/5/EGFP either at the day of birth with analysis at 5 days in vitro, or at 5 days in vitro with analysis at 10 days in vitro. In pyramidal neurons, both TrkB ligands increased dendritic length and number of segments without affecting maximum branch order and number of primary dendrites. In the early time window, only infragranular neurons were responsive. Neurons in layers II/III became responsive to NT4/5, but not BDNF, during the later time window. BDNF and NT4/5 transfectants at 10 days in vitro had still significantly shorter dendrites than adult pyramidal neurons, suggesting a massive growth spurt after 10 days in vitro. However, segment numbers were already in the range of adult neurons. Although this suggested a role for BDNF, long-term activity-deprived, and thus BDNF-deprived, pyramidal cells developed a dendritic complexity not different from neurons in active cultures except for higher spine densities on neurons of layers II/III and VI. Neutralization of endogenous NT4/5 causes shorter and less branched dendrites at 10 days in vitro suggesting an essential role for NT4/5. Neutralization of BDNF had no effect. Transfected multipolar interneurons became identifiable during the second time window. Both TrkB ligands significantly increased number of segments and branch order towards the adult state with little effects on dendritic length. The results suggested that early in development BDNF and NT4/5 probably accelerate dendritogenesis in an autocrine fashion. In particular, branch formation was advanced towards the adult pattern in pyramidal cells and interneurons.     

Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.     

A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex

This study provides a detailed quantitative estimate for local synaptic connectivity between neocortical pyramidal neurons. A new way of obtaining such an estimate is presented. In acute slices of the rat visual cortex, four layer 2 and four layer 3 pyramidal neurons were intracellularly injected with biocytin. Axonal and dendritic arborizations were three-dimensionally reconstructed with the aid of a computer-based camera lucida system. In a computer experiment, pairs of pre- and postsynaptic neurons were formed and potential synaptic contacts were calculated. For each pair, the calculations were carried out for a whole range of distances (0 to 500 μm) between the presynaptic and the postsynaptic neuron, in order to estimate cortical connectivity as a function of the spatial separation of neurons. It was also differentiated whether neurons were situated in the same or in different cortical layers. The data thus obtained was used to compute connection probabilities, the average number of contacts between neurons, the frequency of specific numbers of contacts and the total number of contacts a dendritic tree receives from the surrounding cortical volume. Connection probabilities ranged from 50% to 80% for directly adjacent neurons and from 0% to 15% for neurons 500 μm apart. In many cases, connections were mediated by one contact only. However, close neighbors made on average up to 3 contacts with each other. The question as to whether the method employed in this study yields a realistic estimate of synaptic connectivity is discussed. It is argued that the results can be used as a detailed blueprint for building artificial neural networks with a cortex-like architecture. Received: 30 March 1999 / Accepted in revised form: 5 August 1999     

Ontogenesis of the spine-free initial zone of apical dendrites; studies in cortical pyramidal cells of albino rat]

1. In Golgi-Cox-impregnated coronal sections of albino rat brains at 1, 4, 26, 24, 30, 60 and 90 days it is presented the evolution of the spine-less, bare initial zone ("nude zone", NZ) at the proximal apical main dendrites of the layer V pyramidal neurons in the somatosensory and anterior limbie cortex. The quantitative results are analyzed by statistical methods. 2. The NZ is comprehended as a morphological correlate of the endodendritic neuroplasmic flow (Weiss 1944, Globus, Lux and Schuberl 1968, Kreutzberg 1973). The observed changes of the percental frequency and the average length of NZ increases rapidly. 3. The NZ occurs at first in the (12th) 16 postnatal day, thus in a time, when the organs of hearing and the eyes are differentiated completely. Between 16th and 24th day the percental frequency as well as the longitude of NZ increases. During this time the rats will be independent of the mother animals. With the full differentiation of the urogenital tract and especially with the sexual maturity the percentage frequency of NZ increases only at pyramidal cells in the anterior limbie cortex between 24th and 60th day. During 3rd month the NZ is occuring percental more frequently in the anterior limbic cortex than in the somatosensory cortex. At this time the average length of NZ is shorter in the limbic cortex. 4. As to the enriched, vivid movement of the animals and the playing impulse of the young rats the average length of NZ will be extended at pyramidal neurons in the somatosensory cortex during 2nd month, as well as the pattern of spine distribution will be changed along apical dendrites (Schlerhorn, unpublished). During the following (3rd) month the NZ will be shorteded in the somatosensory cortex, obviously caused by new formation of spines at the proximal main dendrites. 5. These newly formed spines in the initial zone of apical dendrites may be inhibitory spines. The inhibitory spines are stained only when using the mercury chromate impregnation according to Golgi-Cox, but not when using the silver chromate methods according to Golgi-Kopsch or Golgi-Bubenaite. The different tingibility of these spines by different Golgi techniques is discussed by Doedens, Nagel and Schierhorn (1974). The pyramidal neurons in the somatosensory cortex possess a longer average length of NZ (Lnz = 7,3[mum]) than the pyramidal cells in the anterior limbic cortex (Lnz = 6.2[mum]). As to NZ the differences between silver and mercury chromate stained pyramidal neurons are greater in the somatosensory cortex than in limbic cortex (see Tab. 7). Therefore we assume that there are in the initial zone of somatosensory pyramidal neurons more inhibitory spines than at the pyramidal neurons in the anterior limbic cortex. 6. The regional differences in the percentual frequency and in the average length of NZ between somatosensory and limbic cortex are new identifying marks of architectonic differentiation of the pyramidal neurons in cortical regions of phylogenetically different ages.     

Laminar analysis of the origin of the various components of evoked potentials in slices of rat sensorimotor cortex

In slices of rat sensorimotor cortex, extracellular field potentials evoked by electrical stimulation of the white matter were recorded at various cortical depths. In order to determine the nature of the various components, experiments were performed in 3 situations: in a control perfusion medium, in a solution in which calcium ions have been replaced by magnesium ions to block synaptic transmission, and in cortices in which the pyramidal neurons of layer V had been previously induced to degenerate.In the control situation, the response at or near the surface was a positive-negative wave. From a depth of about 150 μm downwards, the evoked response consisted usually of 6 successive components, 3 positive-going, P11, P3 and P6 and 3 negative-going, N2, N4 and N5. P1 and N4 were apparent in superficial layers only. The amplitude of the remaining waves variable in the cortex but all diminished near the white matter.The early part of the surface positive wave arises from a non-synaptic activation of superficial elements, probably apical dendrites. The late part of the surface positive wave and the negative wave are due to the synaptic activation of neurons located probably in layer III.The large negative wave N2 represents principally the antidromic activation of cell bodies and possibly of proximal dendrites of neurons situated in layers III, IV and V, through the compound action potentials of afferent and efferent fibers may contribute to a reduced part to its generation.The late components N4 to P6 are post-synaptic responses. The negative component N5, the amplitude of which is largest in layers III and IV, represents excitatory responses of neurons located at various depths in the cortex. The nature of the positive component P6 is less clear, although the underlying mechanism might be inhibitory synaptic potentials.     

Long-range neuronal circuits underlying the interaction between sensory and motor cortex

In the rodent vibrissal system, active sensation and sensorimotor integration are mediated in part by connections between barrel cortex and vibrissal motor cortex. Little is known about how these structures interact at the level of neurons. We used Channelrhodopsin-2 (ChR2) expression, combined with anterograde and retrograde labeling, to map connections between barrel cortex and pyramidal neurons in mouse motor cortex. Barrel cortex axons preferentially targeted upper layer (L2/3, L5A) neurons in motor cortex; input to neurons projecting back to barrel cortex was particularly strong. Barrel cortex input to deeper layers (L5B, L6) of motor cortex, including neurons projecting to the brainstem, was weak, despite pronounced geometric overlap of dendrites with axons from barrel cortex. Neurons in different layers received barrel cortex input within stereotyped dendritic domains. The cortico-cortical neurons in superficial layers of motor cortex thus couple motor and sensory signals and might mediate sensorimotor integration and motor learning.     

A cooperative switch determines the sign of synaptic plasticity in distal dendrites of neocortical pyramidal neurons

Pyramidal neurons in the cerebral cortex span multiple cortical layers. How the excitable properties of pyramidal neuron dendrites allow these neurons to both integrate activity and store associations between different layers is not well understood, but is thought to rely in part on dendritic backpropagation of action potentials. Here we demonstrate that the sign of synaptic plasticity in neocortical pyramidal neurons is regulated by the spread of the backpropagating action potential to the synapse. This creates a progressive gradient between LTP and LTD as the distance of the synaptic contacts from the soma increases. At distal synapses, cooperative synaptic input or dendritic depolarization can switch plasticity between LTD and LTP by boosting backpropagation of action potentials. This activity-dependent switch provides a mechanism for associative learning across different neocortical layers that process distinct types of information.     

Experience‐dependent plasticity of dendritic spines of layer 2/3 pyramidal neurons in the mouse cortex

Previous studies have shown that sensory and motor experiences play an important role in the remodeling of dendritic spines of layer 5 (L5) pyramidal neurons in the cortex. In this study, we examined the effects of sensory deprivation and motor learning on dendritic spine remodeling of layer 2/3 (L2/3) pyramidal neurons in the barrel and motor cortices. Similar to L5 pyramidal neurons, spines on apical dendrites of L2/3 pyramidal neurons are plastic during development and largely stable in adulthood. Sensory deprivation via whisker trimming reduces the elimination rate of existing spines without significant effect on the rate of spine formation in the developing barrel cortex. Furthermore, we show that motor training increases the formation and elimination of dendritic spines in the primary motor cortex. Unlike L5 pyramidal neurons, however, there is no significant difference in the rate of spine formation between sibling dendritic branches of L2/3 pyramidal neurons. Our studies indicate that sensory and motor learning experiences have important impact on dendritic spine remodeling in L2/3 pyramidal neurons. They also suggest that the rules governing experience‐dependent spine remodeling are largely similar, but not identical, between L2/3 and L5 pyramidal neurons. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 277–286, 2016     

Comparative electron microscopic study of the visual cortex neurons of the cat in postnatal ontogeny

The maturation of layers II-VI of neurons and perineuronal neuropil of the cat visual cortex (field 17) was studied from postnatal day 1 to day 21. The differentiation of large, small (associate) pyramid and stellate neurons was described. During the first postnatal week, the somata of layers II-VI of neurons undergo significant changes, the perikaryal cytoplasm increases in volume. Cell bodies of large pyramidal neurons mature by day 15. During the second postnatal week and almost till day 15, the rough endoplasmic reticulum of small pyramidal and stellate neurons undergoes proliferation; dendritic processes are branching. In stellate neurons the amount of cytoplasmic organelles increases dramatically only after the second postnatal week, and this is presumably induced by the opening of eyes on day 12. The second postnatal week is the period of greatest growth of dendritic, axonal and glial processes in perineural neuropil of layers V-VI. In the perineuronal neuropil of large pyramidal neurons (layers V-VI) there appear symmetric synapses with pyramidal cells, dendritic processes and dendritic spines. This occurs just at the time when kittens first open the eyes. From this time and during postnatal days 15-21, asymmetric synapses appear in the perineuronal neuropil of large pyramidal neurons. In the perineuronal neuropil of small pyramidal and stellate neurons. (layers II-IV), synapses reveal the mature appearance by day 15. After the opening of the eyes and up to postnatal day 21, dendritic growth and spine production occur in the perineuronal neuropil of small pyramidal and stellate neurons.     

Morphology of the cat auditory cortex

The ultrastructural features of the primary auditory cortex of the cats and the character of the endings of geniculo-cortical afferent fibers in the early stages of experimental degeneration evoked by destruction of the medial geniculate body were studied. In all layers of the cortex asymmetrical synapses with round synaptic vesicles on dendritic spines and on thin dendritic branches of pyramidal and nonpyramidal neurons are predominant. Symmetrical synapses with flattened or polymorphic vesicles are distributed chiefly on the bodies of the neurons and their large dendrites. Because there are few symmetrical synapses which could be regarded as inhibitory it is postulated that inhibitory influences may also be transmitted through asymmetrical synapses with round vesicles. Other types of contacts between the bodies of neurons, dendrites, and glial processes also were found in the auditory cortex. Degenerating terminals of geniculo-cortical fibers were shown to terminate chiefly in layer IV of the cortex on pyramidal and nonpyramidal neurons. Degeneration was of the dark type in asymmetrical synapses with round vesicles. The results are dicussed in connection with electrophysiological investigations of the auditory cortex.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 5, pp. 519–524, September–October, 1973.     

M-channels modulate the intrinsic excitability and synaptic responses of layer 2/3 pyramidal neurons in auditory cortex

Neurons in the auditory cortex are believed to utilize temporal patterns of neural activity to accurately process auditory information but the intrinsic neuronal mechanism underlying the control of auditory neural activity is not known. The slowly activating, persistent K⁺ channel, also called M-channel that belongs to the Kv7 family, is already known to be important in regulating subthreshold neural excitability and synaptic summation in neocortical and hippocampal pyramidal neurons. However, its functional role in the primary auditory cortex (A1) has never been characterized. In this study, we investigated the roles of M-channels on neuronal excitability, short-term plasticity, and synaptic summation of A1 layer 2/3 regular spiking pyramidal neurons with whole-cell current-clamp recordings in vitro. We found that blocking M-channels with a selective M-channel blocker, XE991, significantly increased neural excitability of A1 layer 2/3 pyramidal neurons. Furthermore, M-channels controled synaptic responses of intralaminar-evoked excitatory postsynaptic potentials (EPSPs); XE991 significantly increased EPSP amplitude, decreased the rate of short-term depression, and increased the synaptic summation. These results suggest that M-channels are involved in controlling spike output patterns and synaptic responses of A1 layer 2/3 pyramidal neurons, which would have important implications in auditory information processing.     

Spike timing and reliability in cortical pyramidal neurons: effects of EPSC kinetics, input synchronization and background noise on spike timing

In vivo studies have shown that neurons in the neocortex can generate action potentials at high temporal precision. The mechanisms controlling timing and reliability of action potential generation in neocortical neurons, however, are still poorly understood. Here we investigated the temporal precision and reliability of spike firing in cortical layer V pyramidal cells at near-threshold membrane potentials. Timing and reliability of spike responses were a function of EPSC kinetics, temporal jitter of population excitatory inputs, and of background synaptic noise. We used somatic current injection to mimic population synaptic input events and measured spike probability and spike time precision (STP), the latter defined as the time window (Deltat) holding 80% of response spikes. EPSC rise and decay times were varied over the known physiological spectrum. At spike threshold level, EPSC decay time had a stronger influence on STP than rise time. Generally, STP was highest (6 ms) triggered spikes at lower temporal precision (>or=6.58 ms). We found an overall linear relationship between STP and spike delay. The difference in STP between fast and slow compound EPSCs could be reduced by incrementing the amplitude of slow compound EPSCs. The introduction of a temporal jitter to compound EPSCs had a comparatively small effect on STP, with a tenfold increase in jitter resulting in only a five fold decrease in STP. In the presence of simulated synaptic background activity, precisely timed spikes could still be induced by fast EPSCs, but not by slow EPSCs.     

Enhancement of spike-timing precision by autaptic transmission in neocortical inhibitory interneurons

In vivo studies suggest that precise firing of neurons is important for correct sensory representation. Principal neocortical neurons fire imprecisely when repeatedly activated by fixed sensory stimuli or current depolarizations. Here we show that in contrast to pyramidal neurons, firing in neocortical GABAergic fast-spiking (FS) interneurons is quite precise. FS interneurons are self-innervated by powerful GABAergic autaptic connections reliably activated after each spike, suggesting that autapses strongly regulate FS-cell spike timing. Indeed, blockade of autaptic transmission degraded temporal precision in multiple ways. Under these conditions, realistic dynamic-clamp hyperpolarizing autapses restored precision of spike timing, even in the presence of synaptic noise. Furthermore, firing precision was increased in pyramidal neurons by artificial GABAergic autaptic conductances, suggesting that tightly coupled synaptic feedback inhibition regulates spike timing in principal cells. Thus, well-timed inhibition, whether autaptic or synaptic, facilitates precise spike timing and promotes synchronized cortical network oscillations relevant to several behaviors.