RESUMO
Coincidence detection and cortical rhythmicity are both greatly influenced by neurons' propensity to fire bursts of action potentials. In the neocortex, repetitive burst firing can also initiate abnormal neocortical rhythmicity (including epilepsy). Bursts are generated by inward currents that underlie a fast afterdepolarization (fADP) but less is known about outward currents that regulate bursting. We tested whether Kv2 channels regulate the fADP and burst firing in labeled layer 5 PNs from motor cortex of the Thy1-h mouse. Kv2 block with guangxitoxin-1E (GTx) converted single spike responses evoked by dendritic stimulation into multispike bursts riding on an enhanced fADP. Immunohistochemistry revealed that Thy1-h PNs expressed Kv2.1 (not Kv2.2) channels perisomatically (not in the dendrites). In somatic macropatches, GTx-sensitive current was the largest component of outward current with biophysical properties well-suited for regulating bursting. GTx drove ~40% of Thy1 PNs stimulated with noisy somatic current steps to repetitive burst firing and shifted the maximal frequency-dependent gain. A network model showed that reduction of Kv2-like conductance in a small subset of neurons resulted in repetitive bursting and entrainment of the circuit to seizure-like rhythmic activity. Kv2 channels play a dominant role in regulating onset bursts and preventing repetitive bursting in Thy1 PNs.
Assuntos
Neocórtex , Canais de Potássio Shab , Potenciais de Ação/fisiologia , Animais , Camundongos , Neocórtex/metabolismo , Neurônios/fisiologia , Células Piramidais/fisiologia , Canais de Potássio Shab/metabolismoRESUMO
Anion channels and connexin hemichannels are permeable to amino acid neurotransmitters. It is hypothesized that these conductive pathways release GABA, thereby influencing ambient GABA levels and tonic GABAergic inhibition. To investigate this, we measured the effects of anion channel/hemichannel antagonists on tonic GABA currents of rat hippocampal neurons. In contrast to predictions, blockade of anion channels and hemichannels with NPPB potentiated tonic GABA currents of neurons in culture and acute hippocampal slices. In contrast, the anion channel/hemichannel antagonist carbenoxolone (CBX) inhibited tonic currents. These findings could result from alterations of ambient GABA concentration or direct effects on GABAA receptors. To test for effects on GABAA receptors, we measured currents evoked by exogenous GABA. Coapplication of NPPB with GABA potentiated GABA-evoked currents. CBX dose-dependently inhibited GABA-evoked currents. These results are consistent with direct effects of NPPB and CBX on GABAA receptors. GABA release from hippocampal cell cultures was directly measured using HPLC. Inhibition of anion channels with NPPB or CBX did not affect GABA release from cultured hippocampal neurons. NPPB reduced GABA release from pure astrocytic cultures by 21%, but the total GABA release from astrocytes was small compared to that of mixed cultures. These data indicate that drugs commonly used to antagonize anion channels and connexin hemichannels may affect tonic currents via direct effects on GABAA receptors and have negligible effects on ambient GABA concentrations. Interpretation of experiments using NPPB or CBX should include consideration of their effects on tonic GABA currents.
Assuntos
Conexinas/antagonistas & inibidores , Conexinas/fisiologia , Antagonistas de Receptores de GABA-A/farmacologia , Receptores de GABA-A/fisiologia , Canais de Ânion Dependentes de Voltagem/antagonistas & inibidores , Canais de Ânion Dependentes de Voltagem/fisiologia , Aminobenzoatos/farmacologia , Animais , Animais Recém-Nascidos , Carbenoxolona/farmacologia , Células Cultivadas , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Nitrobenzoatos/farmacologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/farmacologiaRESUMO
Ambient GABA in the brain tonically activates extrasynaptic GABA(A) receptors, and activity-dependent changes in ambient GABA concentration can also activate GABA(B) receptors. To investigate an interaction between postsynaptic GABA(B) and GABA(A) receptors, we recorded GABA(A) currents elicited by exogenous GABA (10 µm) from dentate gyrus granule cells (DGGCs) in adult rat hippocampal slices. The GABA(B) receptor agonist baclofen (20 µm) enhanced GABA(A) currents. This enhancement was blocked by the GABA(B) receptor antagonist CGP 55845 and intracellular solutions containing the GTP analog GDP-ß-s, indicating that baclofen was acting on postsynaptic GABA(B) receptors. Modulation of GABA(A) currents by postsynaptic GABA(B) receptors was not observed in CA1 pyramidal cells or layer 2/3 cortical pyramidal neurons. Baclofen reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not alter sIPSC amplitude or kinetics. Thus, GABA(A) receptors activated at synapses were not modulated by postsynaptic GABA(B) receptors. In contrast, tonic GABA currents and currents activated by the GABA(A) receptor δ subunit-selective agonist THIP (10 µm) were potentiated by baclofen. Our data indicate that postsynaptic GABA(B) receptors enhance the function of extrasynaptic GABA(A) receptors, including δ subunit-containing receptors that mediate tonic inhibition in DGGCs. The modulation of GABA(A) receptor function by postsynaptic GABA(B) receptors is a newly identified mechanism that will influence the inhibitory tone of DGGCs when GABA(B) and GABA(A) receptors are both activated.
Assuntos
Giro Denteado/citologia , Neurônios/fisiologia , Sinapses/metabolismo , Animais , Biofísica , Interações Medicamentosas , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Feminino , GABAérgicos/farmacologia , Guanosina Difosfato/análogos & derivados , Guanosina Difosfato/farmacologia , Guanosina Trifosfato/farmacologia , Técnicas In Vitro , Macrolídeos/farmacologia , Masculino , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Tionucleotídeos/farmacologia , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
While adaptation is widely thought to facilitate neural coding, the form of adaptation should depend on how the signals are encoded. Monaural neurons early in the interaural time difference (ITD) pathway encode the phase of sound input using spike timing rather than firing rate. Such neurons in chicken nucleus magnocellularis (NM) adapt to ongoing stimuli by increasing firing rate and decreasing spike timing precision. We measured NM neuron responses while adapting them to simulated physiological input, and used these responses to construct inputs to binaural coincidence detector neurons in nucleus laminaris (NL). Adaptation of spike timing in NM reduced ITD sensitivity in NL, demonstrating the dominant role of timing in the short-term plasticity as well as the immediate response of this sound localization circuit.
Assuntos
Adaptação Fisiológica/fisiologia , Tronco Encefálico/fisiologia , Localização de Som/fisiologia , Estimulação Acústica , Algoritmos , Animais , Vias Auditivas/fisiologia , Núcleo Basal de Meynert/fisiologia , Embrião de Galinha , Núcleo Coclear/citologia , Núcleo Coclear/fisiologia , Fenômenos Eletrofisiológicos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Lateralidade Funcional/fisiologia , Canal de Potássio Kv1.1/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/farmacologia , Tetrodotoxina/farmacologiaRESUMO
Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by 1) transient increases in extracellular GABA concentration ([GABA]), 2) transient postsynaptic depolarization, and 3) depolarization of presynaptic cells. Transient increases in [GABA] (1 µM) reduced tonic currents; this reduction resulted from GABA-induced shifts in the reversal potential for GABA currents (E(GABA)). Transient depolarization of postsynaptic neurons reversed the effects of exogenous GABA and potentiated tonic currents. The voltage-dependent potentiation of tonic GABA currents was independent of E(GABA) shifts and represented postdepolarization potentiation (PDP), an intrinsic GABA(A) receptor property (Ransom CB, Wu Y, Richerson GB. J Neurosci 30: 7672-7684, 2010). Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect tonic currents. In ConA-treated cells, transient application of 12 mM K(+) to depolarize presynaptic neurons and glia produced a persistent increase in tonic current amplitude. The K(+)-induced increase in tonic current was reversibly inhibited by SKF89976a (40 µM), indicating that this was caused by nonvesicular GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due to GAT1 reversal also occurred in acute hippocampal brain slices. Our results indicate that tonic GABA currents are rapidly regulated by GABA-induced changes in intracellular Cl(-) concentration, PDP of extrasynaptic GABA(A) receptors, and nonvesicular GABA release. These mechanisms may influence tonic inhibition during seizures when neurons are robustly depolarized and extracellular GABA and K(+) concentrations are elevated.
Assuntos
Potenciais de Ação , Hipocampo/fisiologia , Neurônios/fisiologia , Potenciais Sinápticos , Ácido gama-Aminobutírico/metabolismo , Animais , Cloretos/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Neuroglia/fisiologia , Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Receptores de GABA-A/fisiologia , Sinapses/metabolismo , Sinapses/fisiologiaRESUMO
Elucidating how neurons encode network activity is essential to understanding how the brain processes information. Neocortical pyramidal cells receive excitatory input onto spines distributed along dendritic branches. Local dendritic branch nonlinearities can boost the response to spatially clustered and synchronous input, but how this translates into the integration of patterns of ongoing activity remains unclear. To examine dendritic integration under naturalistic stimulus regimes, we use two-photon glutamate uncaging to repeatedly activate multiple dendritic spines at random intervals. In the proximal dendrites of two populations of layer 5 pyramidal neurons in the mouse motor cortex, spatially restricted synchrony is not a prerequisite for dendritic boosting. Branches encode afferent inputs with distinct rate sensitivities depending upon cell and branch type. Thus, inputs distributed along a dendritic branch can recruit supralinear boosting and the window of this nonlinearity may provide a mechanism by which dendrites can preferentially amplify slow-frequency network oscillations.
Assuntos
Dendritos/fisiologia , Neocórtex/fisiologia , Células Piramidais/fisiologia , Potenciais de Ação/fisiologia , Animais , Espinhas Dendríticas/fisiologia , Feminino , Masculino , Camundongos TransgênicosRESUMO
Activation of postsynaptic GABA-B receptors enhances tonic inhibition mediated by high-affinity extrasynaptic GABAA receptors in dentate gyrus granule cells (DGGCs), thalamocortical neurons, and cerebellar granule cells. We investigated the mechanism(s) of GABA current modulation by GABAB receptors in DGGCs using a combination of electrophysiological and biochemical approaches. In acute hippocampal brain slices the GABAB receptor agonist baclofen increased GABA-evoked currents in â¼2/3rds of DGGCs, significantly increasing GABAA currents by 41% on average. Nonstationary noise analysis was performed to estimate the effects of baclofen on single channel conductance, mean open time, and channel number; these estimates suggest that GABAB receptor activation increases receptor number but does not modify single channel properties of GABAA receptors. To directly assess baclofen-induced changes in plasma membrane expression of GABAA receptors, biotinylated western blots were performed. Treatment of hippocampal slices with baclofen significantly increased the surface expression of GABAA receptor subunits (both δ and γ2 subunits) and this effect was inhibited by the GABAB receptor antagonist CGP55845. These data indicate that changes in membrane trafficking and increased number of GABAA receptors in plasma membrane contribute to the enhancement of GABA currents produced by GABAB receptor activation in DGGCs.
Assuntos
Receptores de GABA-A , Receptores de GABA-B , Animais , Baclofeno/farmacologia , Encéfalo/metabolismo , Giro Denteado/metabolismo , Antagonistas de Receptores de GABA-B/farmacologia , Neurônios/metabolismo , Ratos , Receptores de GABA-A/metabolismo , Receptores de GABA-B/metabolismo , Sinapses/fisiologiaRESUMO
Previous studies showed that cortical pyramidal neurones (PNs) have a dynamic spike threshold that functions as a high-pass filter, enhancing spike timing in response to high-frequency input. While it is commonly assumed that Na(+) channel inactivation is the primary mechanism of threshold accommodation, the possible role of K(+) channel activation in fast threshold changes has not been well characterized. The present study tested the hypothesis that low-voltage activated Kv1 channels affect threshold dynamics in layer 2-3 PNs, using α-dendrotoxin (DTX) or 4-aminopyridine (4-AP) to block these conductances. We found that Kv1 blockade reduced the dynamic changes of spike threshold in response to a variety of stimuli, including stimulus-evoked synaptic input, current steps and ramps of varied duration, and noise. Analysis of the responses to noise showed that Kv1 channels increased the coherence of spike output with high-frequency components of the stimulus. A simple model demonstrates that a dynamic spike threshold can account for this effect. Our results show that the Kv1 conductance is a major mechanism that contributes to the dynamic spike threshold and precise spike timing of cortical PNs.
Assuntos
Córtex Motor/fisiologia , Células Piramidais/fisiologia , Superfamília Shaker de Canais de Potássio/fisiologia , 4-Aminopiridina/farmacologia , Animais , Venenos Elapídicos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Técnicas In Vitro , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superfamília Shaker de Canais de Potássio/antagonistas & inibidoresRESUMO
The frequency response properties of neurons are critical for signal transmission and control of network oscillations. At subthreshold membrane potential, some neurons show resonance caused by voltage-gated channels. During action potential firing, resonance of the spike output may arise from subthreshold mechanisms and/or spike-dependent currents that cause afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs). Layer 2-3 pyramidal neurons (L2-3 PNs) have a fast ADP that can trigger bursts. The present study investigated what stimuli elicit bursting in these cells and whether bursts transmit specific frequency components of the synaptic input, leading to resonance at particular frequencies. We found that two-spike bursts are triggered by step onsets, sine waves in two frequency bands, and noise. Using noise adjusted to elicit firing at approximately 10 Hz, we measured the gain for modulation of the time-varying firing rate as a function of stimulus frequency, finding a primary peak (7-16 Hz) and a high-frequency resonance (250-450 Hz). Gain was also measured separately for single and burst spikes. For a given spike rate, bursts provided higher gain at the primary peak and lower gain at intermediate frequencies, sharpening the high-frequency resonance. Suppression of bursting using automated current feedback weakened the primary and high-frequency resonances. The primary resonance was also influenced by the SK channel-mediated medium AHP (mAHP), because the SK blocker apamin reduced the sharpness of the primary peak. Our results suggest that resonance in L2-3 PNs depends on burst firing and the mAHP. Bursting enhances resonance in two distinct frequency bands.
Assuntos
Potenciais de Ação/fisiologia , Neocórtex/citologia , Neocórtex/fisiologia , Células Piramidais/fisiologia , Animais , Retroalimentação/fisiologia , Membro Anterior/citologia , Membro Anterior/fisiologia , Membro Posterior/citologia , Membro Posterior/fisiologia , Masculino , Modelos Neurológicos , Condução Nervosa/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-DawleyRESUMO
Nucleus laminaris (NL) neurons encode interaural time difference (ITD), the cue used to localize low-frequency sounds. A physiologically based model of NL input suggests that ITD information is contained in narrow frequency bands around harmonics of the sound frequency. This suggested a theory, which predicts that, for each tone frequency, there is an optimal time course for synaptic inputs to NL that will elicit the largest modulation of NL firing rate as a function of ITD. The theory also suggested that neurons in different tonotopic regions of NL require specialized tuning to take advantage of the input gradient. Tonotopic tuning in NL was investigated in brain slices by separating the nucleus into three regions based on its anatomical tonotopic map. Patch-clamp recordings in each region were used to measure both the synaptic and the intrinsic electrical properties. The data revealed a tonotopic gradient of synaptic time course that closely matched the theoretical predictions. We also found postsynaptic band-pass filtering. Analysis of the combined synaptic and postsynaptic filters revealed a frequency-dependent gradient of gain for the transformation of tone amplitude to NL firing rate modulation. Models constructed from the experimental data for each tonotopic region demonstrate that the tonotopic tuning measured in NL can improve ITD encoding across sound frequencies.
Assuntos
Modelos Neurológicos , Neurônios/fisiologia , Localização de Som/fisiologia , Sinapses/fisiologia , Estimulação Acústica , Potenciais de Ação , Animais , Embrião de Galinha , Galinhas , Simulação por Computador , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores , Técnicas In Vitro , Potenciais da Membrana , Vias Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Transmissão Sináptica/fisiologia , Temperatura , Fatores de TempoRESUMO
Voltage-gated sodium channels (Na(V)) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI). Homozygous null Scn1a-/- mice developed ataxia and died on postnatal day (P) 15 but could be sustained to P17.5 with manual feeding. Heterozygous Scn1a+/- mice had spontaneous seizures and sporadic deaths beginning after P21, with a notable dependence on genetic background. Loss of Na(V)1.1 did not change voltage-dependent activation or inactivation of sodium channels in hippocampal neurons. The sodium current density was, however, substantially reduced in inhibitory interneurons of Scn1a+/- and Scn1a-/- mice but not in their excitatory pyramidal neurons. An immunocytochemical survey also showed a specific upregulation of Na(V)1.3 channels in a subset of hippocampal interneurons. Our results indicate that reduced sodium currents in GABAergic inhibitory interneurons in Scn1a+/- heterozygotes may cause the hyperexcitability that leads to epilepsy in patients with SMEI.
Assuntos
Potenciais de Ação/fisiologia , Epilepsias Mioclônicas/fisiopatologia , Interneurônios/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Canais de Sódio/fisiologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Eletroencefalografia , Epilepsias Mioclônicas/genética , Genótipo , Humanos , Immunoblotting , Lactente , Interneurônios/citologia , Interneurônios/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.1 , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Técnicas de Patch-Clamp , Fenótipo , Convulsões/genética , Convulsões/mortalidade , Convulsões/fisiopatologia , Canais de Sódio/genética , Canais de Sódio/metabolismo , Taxa de Sobrevida , Ácido gama-Aminobutírico/metabolismoRESUMO
Adaptation is commonly defined as a decrease in response to a constant stimulus. In the auditory system such adaptation is seen at multiple levels. However, the first-order central neurons of the interaural time difference detection circuit encode information in the timing of spikes rather than the overall firing rate. We investigated adaptation during in vitro whole-cell recordings from chick nucleus magnocellularis neurons. Injection of noisy, depolarizing current caused an increase in firing rate and a decrease in spike time precision that developed over approximately 20 s. This adaptation depends on sustained depolarization, is independent of firing, and is eliminated by alpha-dendrotoxin (0.1 microM), implicating slow inactivation of low-threshold voltage-activated K+ channels as its mechanism. This process may alter both firing rate and spike-timing precision of phase-locked inputs to coincidence detector neurons in nucleus laminaris and thereby adjust the precision of sound localization.
Assuntos
Potenciais de Ação/fisiologia , Adaptação Fisiológica/fisiologia , Aves/fisiologia , Núcleo Coclear/fisiologia , Neurônios/fisiologia , Localização de Som/fisiologia , Estimulação Acústica , Animais , Percepção Auditiva/fisiologia , Aves/anatomia & histologia , Embrião de Galinha , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Canais de Potássio/fisiologia , Tempo de Reação/fisiologia , Transmissão Sináptica/fisiologia , Fatores de TempoRESUMO
Neuronal responses are often characterized by the firing rate as a function of the stimulus mean, or the f-I curve. We introduce a novel classification of neurons into Types A, B-, and B+ according to how f-I curves are modulated by input fluctuations. In Type A neurons, the f-I curves display little sensitivity to input fluctuations when the mean current is large. In contrast, Type B neurons display sensitivity to fluctuations throughout the entire range of input means. Type B- neurons do not fire repetitively for any constant input, whereas Type B+ neurons do. We show that Type B+ behavior results from a separation of time scales between a slow and fast variable. A voltage-dependent time constant for the recovery variable can facilitate sensitivity to input fluctuations. Type B+ firing rates can be approximated using a simple "energy barrier" model.
Assuntos
Sistema Nervoso Central/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Animais , Membrana Celular/fisiologia , Simulação por Computador , Humanos , Potenciais da Membrana/fisiologia , Fatores de TempoRESUMO
Neuronal firing is known to depend on the variance of synaptic input as well as the mean input current. Several studies suggest that input variance, or "noise," has a divisive effect, reducing the slope or gain of the firing frequency-current (f-I) relationship. We measured the effects of current noise on f-I relationships in pyramidal neurons and fast-spiking (FS) interneurons in slices of rat sensorimotor cortex. In most pyramidal neurons, noise had a multiplicative effect on the steady-state f-I relationship, increasing gain. In contrast, noise reduced gain in FS interneurons. Gain enhancement in pyramidal neurons increased with stimulus duration and was correlated with the amplitude of the slow afterhyperpolarization (sAHP), a major mechanism of spike-frequency adaptation. The 5-HT2 receptor agonist alpha-methyl-5-HT reduced the sAHP and eliminated gain increases, whereas augmenting the sAHP conductance by spike-triggered dynamic-current clamp enhanced the gain increase. These results indicate that the effects of noise differ fundamentally between classes of neocortical neurons, depending on specific biophysical properties including the sAHP conductance. Thus, noise from background synaptic input may enhance network excitability by increasing gain in pyramidal neurons with large sAHPs and reducing gain in inhibitory FS interneurons.
Assuntos
Neocórtex/fisiologia , Neurônios/fisiologia , Potenciais de Ação , Animais , Artefatos , Condutividade Elétrica , Estimulação Elétrica/métodos , Técnicas In Vitro , Interneurônios/fisiologia , Neocórtex/citologia , Técnicas de Patch-Clamp , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação , Agonistas do Receptor de Serotonina/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Fatores de TempoRESUMO
Avian nucleus magnocellularis (NM) spikes provide a temporal code representing sound arrival times to downstream neurons that compute sound source location. NM cells act as high-pass filters by responding only to discrete synaptic events while ignoring temporally summed EPSPs. This high degree of input selectivity insures that each output spike from NM unambiguously represents inputs that contain precise temporal information. However, we lack a quantitative description of the computation performed by NM cells. A powerful model for predicting output firing rate given an arbitrary current input is given by a linear/nonlinear cascade: the stimulus is compared with a known relevant feature by linear filtering, and based on that comparison, a nonlinear function predicts the firing response. Spike-triggered covariance analysis allows us to determine a generalization of this model in which firing depends on more than one spike-triggering feature or stimulus dimension. We found two current features relevant for NM spike generation; the most important simply smooths the current on short time scales, whereas the second confers sensitivity to rapid changes. A model based on these two features captured more mutual information between current and spikes than a model based on a single feature. We used this analysis to characterize the changes in the computation brought about by pharmacological manipulation of the biophysical properties of the neurons. Blockage of low-threshold voltage-gated potassium channels selectively eliminated the requirement for the second stimulus feature, generalizing our understanding of input selectivity by NM cells. This study demonstrates the power of covariance analysis for investigating single neuron computation.
Assuntos
Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Animais , Embrião de Galinha , Venenos Elapídicos/farmacologia , Estimulação Elétrica/métodos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Técnicas In Vitro , Neurônios/efeitos dos fármacos , Neurotoxinas/farmacologia , Dinâmica não Linear , Distribuição Normal , Fatores de TempoRESUMO
The firing rate of neocortical pyramidal neurons is believed to represent primarily the average arrival rate of synaptic inputs; however, it has also been found to vary somewhat depending on the degree of synchrony among synaptic inputs. We investigated the ability of pyramidal neurons to perform coincidence detection, that is, to represent input timing in their firing rate, and explored some factors that influence that representation. We injected computer-generated simulated synaptic inputs into pyramidal neurons during whole-cell recordings, systematically altering the phase delay between two groups of periodic simulated input events. We explored how input intensity, the synaptic time course, inhibitory synaptic conductance, and input jitter influenced the firing rate representation of input timing. In agreement with computer modeling studies, we found that input synchronization increases firing rate when intensity is low but reduces firing rate when intensity is high. At high intensity, the effect of synchrony on firing rate could be switched from reducing to increasing firing rate by shortening the simulated excitatory synaptic time course, adding inhibition (using the dynamic clamp technique), or introducing a small input jitter. These opposite effects of synchrony may serve different computational functions: as a means of increasing firing rate it may be useful for efficient recruitment or for computing a continuous parameter, whereas as a means of decreasing firing rate it may provide gain control, which would allow redundant or excessive input to be ignored. Modulation of dynamic input properties may allow neurons to perform different operations depending on the task at hand.
Assuntos
Neocórtex/fisiologia , Células Piramidais/fisiologia , Animais , Simulação por Computador , Estimulação Elétrica , Técnicas In Vitro , Modelos Neurológicos , Neocórtex/citologia , Inibição Neural/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Córtex Somatossensorial/citologia , Córtex Somatossensorial/fisiologiaRESUMO
Human listeners' sensitivity to interaural time differences (ITD) was assessed for 1000 Hz tone bursts (500 ms duration) preceded by trains of 500-ms "adapter" tone bursts (7 s total adapter duration, frequencies of 200, 665, 1000, or 1400 Hz) carrying random ITD, or by an equal-duration period of silence. Presentation of the adapter burst train reduced ITD sensitivity in a frequency-specific manner. The observed effect differs from previously described forms of location-specific psychophysical adaptation, as it was produced using a binaurally diffuse sequence of tone bursts (i.e., a location-nonspecific adapter stimulus). Results are discussed in the context of pre-binaural adaptation.
Assuntos
Percepção Auditiva/fisiologia , Localização de Som/fisiologia , Estimulação Acústica , Adaptação Fisiológica , Limiar Auditivo/fisiologia , Humanos , Psicoacústica , Fatores de TempoRESUMO
Neurons in the mammalian neocortex receive inputs from and communicate back to thousands of other neurons, creating complex spatiotemporal activity patterns. The experimental investigation of these parallel dynamic interactions has been limited due to the technical challenges of monitoring or manipulating neuronal activity at that level of complexity. Here we describe a new massively parallel photostimulation system that can be used to control action potential firing in in vitro brain slices with high spatial and temporal resolution while performing extracellular or intracellular electrophysiological measurements. The system uses digital light processing technology to generate 2-dimensional (2D) stimulus patterns with >780,000 independently controlled photostimulation sites that operate at high spatial (5.4 µm) and temporal (>13 kHz) resolution. Light is projected through the quartz-glass bottom of the perfusion chamber providing access to a large area (2.76 mm × 2.07 mm) of the slice preparation. This system has the unique capability to induce temporally precise action potential firing in large groups of neurons distributed over a wide area covering several cortical columns. Parallel photostimulation opens up new opportunities for the in vitro experimental investigation of spatiotemporal neuronal interactions at a broad range of anatomical scales.
RESUMO
Neural systems adapt to changes in stimulus statistics. However, it is not known how stimuli with complex temporal dynamics drive the dynamics of adaptation and the resulting firing rate. For single neurons, it has often been assumed that adaptation has a single time scale. We found that single rat neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics. This multiple time scale adaptation is consistent with fractional order differentiation, such that the neuron's firing rate is a fractional derivative of slowly varying stimulus parameters. Biophysically, even though neuronal fractional differentiation effectively yields adaptation with many time scales, we found that its implementation required only a few properly balanced known adaptive mechanisms. Fractional differentiation provides single neurons with a fundamental and general computation that can contribute to efficient information processing, stimulus anticipation and frequency-independent phase shifts of oscillatory neuronal firing.
Assuntos
Diferenciação Celular/fisiologia , Neocórtex/citologia , Células Piramidais/fisiologia , Potenciais de Ação/fisiologia , Adaptação Fisiológica/fisiologia , Análise de Variância , Animais , Estimulação Elétrica/métodos , Eletrodos , Técnicas In Vitro , Modelos Neurológicos , Dinâmica não Linear , Técnicas de Patch-Clamp/métodos , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
A depressing synapse transforms a time interval into a voltage amplitude. The effect of that transformation on the output of the neuron and network depends on the kinetics of synaptic depression and properties of the postsynaptic neuron and network. Using as examples neural circuits that incorporate depressing synapses, we show how short-term depression can contribute to a surprising variety of time-dependent computational and behavioral tasks.