Properties of convergent thalamocortical and intracortical synaptic potentials in single neurons of neocortex (original) (raw)
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Postsynaptic Mechanisms Govern the Differential Excitation of Cortical Neurons by Thalamic Inputs
Journal of Neuroscience, 2009
Thalamocortical (TC) afferents relay sensory input to the cortex by making synapses onto both excitatory regular-spiking principal cells (RS cells) and inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial role in coordinating excitation with inhibition during the earliest steps of somatosensory processing in the cortex. Although the same TC afferents contact both FS and RS cells, FS cells receive larger and faster excitatory inputs from individual TC afferents. Here, we show that this larger thalamic excitation of FS cells occurs via GluR2-lacking AMPA receptors (AMPARs), and results from a fourfold larger quantal amplitude compared with the thalamic inputs onto RS cells. Thalamic afferents also activate NMDA receptors (NMDARs) at synapses onto both cells types, yet RS cell NMDAR currents are slower and pass more current at physiological membrane potentials. Because of these synaptic specializations, GluR2lacking AMPARs selectively maintain feedforward inhibition of RS cells, whereas NMDARs contribute to the spiking of RS cells and hence to cortical recurrent excitation. Thus, thalamic afferent activity diverges into two routes that rely on unique complements of postsynaptic AMPARs and NMDARs to orchestrate the dynamic balance of excitation and inhibition as sensory input enters the cortex.
The Journal of Physiology, 2010
Thalamocortical afferents innervate both excitatory and inhibitory cells, the latter in turn producing disynaptic feedforward inhibition, thus creating fast excitation-inhibition sequences in the cortical cells. Since this inhibition is disynaptic, the time lag of the excitation-inhibition sequence could be ∼2-3 ms, while it is often as short as only slightly above 1 ms; the mechanism and function of such fast IPSPs are not fully understood. Here we show that thalamic activation of inhibitory neurons precedes that of excitatory neurons, due to increased conduction velocity of thalamic axons innervating inhibitory cells. Developmentally, such latency differences were seen only after the end of the second postnatal week, prior to the completion of myelination of the thalamocortical afferent. Furthermore, destroying myelination failed to extinguish the latency difference. Instead, axons innervating inhibitory cells had consistently lower threshold, indicating they had larger diameter, which is likely to underlie the differential conduction velocity. Since faster activation of GABAergic neurons from the thalamus can not only curtail monosynaptic EPSPs but also make disynaptic ISPSs precede disynaptic EPSPs, such suppression theoretically enables a temporal separation of thalamically driven mono-and disynaptic EPSPs, resulting in spike sequences of 'L4 leading L2/3'. By recording L4 and L2/3 cells simultaneously, we found that suppression of IPSPs could lead to deterioration of spike sequences. Thus, from the end of the second postnatal week, by activating GABAergic neurons prior to excitatory neurons from the thalamus, fast feedforward disynaptic suppression on postsynaptic cells may play a role in establishing the spike sequences of 'L4 leading L2/3 cells'.
Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs
Science (New York, N.Y.), 1997
Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning. In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs. Their average amplitudes were differentially up- or down-regulated, depending on the precise timing of postsynaptic APs relative to EPSPs. These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons.
Feedforward Inhibitory Control of Sensory Information in Higher-Order Thalamic Nuclei
Journal of Neuroscience, 2005
Sensory stimuli evoke strong responses in thalamic relay cells, which ensure a faithful relay of information to the neocortex. However, relay cells of the posterior thalamic nuclear group in rodents, despite receiving significant trigeminal input, respond poorly to vibrissa deflection. Here we show that sensory transmission in this nucleus is impeded by fast feedforward inhibition mediated by GABAergic neurons of the zona incerta. Intracellular recordings of posterior group neurons revealed that the first synaptic event after whisker deflection is a prominent inhibition. Whisker-evoked EPSPs with fast rise time and longer onset latency are unveiled only after lesioning the zona incerta. Excitation survives barrel cortex lesion, demonstrating its peripheral origin. Electron microscopic data confirm that trigeminal axons make large synaptic terminals on the proximal dendrites of posterior group cells and on the somata of incertal neurons. Thus, the connectivity of the system allows an unusual situation in which inhibition precedes ascending excitation resulting in efficient shunting of the responses. The dominance of inhibition over excitation strongly suggests that the paralemniscal pathway is not designed to relay inputs triggered by passive whisker deflection. Instead, we propose that this pathway operates through disinhibition, and that the posterior group forwards to the cerebral cortex sensory information that is contingent on motor instructions.
1999
Amplitudes of EPSPs evoked by repetitive presynaptic action potentials can either decrease (synaptic depression) or increase (synaptic facilitation). To determine whether facilitation and depression in the connections between neocortical pyramidal cells varied with the identity of the pre-or the postsynaptic cell and whether they changed during postnatal development, whole-cell voltage recordings were made simultaneously from two or three pyramidal cells in layers 2/3 and 5 of the rat sensorimotor cortex. Unitary EPSPs were evoked when preand postsynaptic neurons were in the same and in different layers. In young [postnatal day 14 (P14)] cortex, EPSPs evoked in all connected neurons depressed. The degree of depression was layer specific and was determined by the identity of the presynaptic cell. EPSPs evoked by stimulation of presynaptic layer 5 neurons depressed significantly more than did those evoked by stimulation of layer 2/3 neurons. In mature cortex (P28), however, the EPSPs evoked in these connected neurons facilitated to a comparable degree regardless of the layer in which pre-and postsynaptic neurons were located. The results suggest that in young cortex the degree of synaptic depression in connected pyramidal cells is determined primarily by whether the presynaptic cell was in layer 2/3 or 5 and that maturation of the cortex involves a developmental switch from depression to facilitation between P14 and P28 that eliminates the layerspecific differences. A functional consequence of this switch is that in mature cortex the spread of excitation between neocortical pyramidal neurons is enhanced when action potentials occur in bursts.
Efficacy of Thalamocortical and Intracortical Synaptic Connections
Neuron, 1999
connections from thalamus to cortex are significantly of each input to the construction of receptive field propmore effective than IC connections; although quantal erties in primary sensory areas of cortex is unclear. This size is the same in the two tracts, TC connections have issue has been intensively investigated for orientation a higher innervation ratio and release probability than selectivity in visual cortex. Some studies have con-IC connections. cluded that spatially aligned TC inputs alone account for orientation selectivity, while others suggest that recurrent IC circuits provide essential enhancement of Results weak TC inputs (for discussions, see Hubel and Wiesel, 1962; Douglas et al., 1995; Reid and Alonso, 1995, 1996; Our basic strategy was to record from single spiny neurons of the primary somatosensory (barrel) cortex in vitro and independently measure the properties of TC and IC inputs to each cell (Gil and Amitai, 1996; Gil et ‡ To whom correspondence should be addressed (e-mail: barry_ connors@brown.edu). al., 1997). The biocytin-stained cells we recovered (n ϭ Neuron 386 Gil and Amitai, 1996; Gil et al., 1997). Crossed paired pulses were References used to verify that stimuli of one tract were not contaminated by activation of axons from the other tract (Gil et al., 1997). In some Abdul-Ghani, M.A., Valiante, T.A., and Pennefather, P.S. (1996). Sr 2ϩ and quantal events at excitatory synapses between mouse hippo-experiments, biocytin (0.1%) was included in the pipette solution, and the slices were processed by standard avidin-biotin-peroxidase campal neurons in culture. J. Physiol. (Lond.) 495, 113-125. procedures (Horikawa and Armstrong, 1988). Agmon, A., and Connors, B.W. (1991). Thalamocortical responses The transmitter receptor blockers bicuculline methiodide (BMI, 5 of mouse somatosensory (barrel) cortex in vitro. Neuroscience 41, M; RBI), D,L-2-amino-5-phosphonovalerate (APV, 30 M; RBI), 6,7-365-379. dinitroquinoxaline-2,3-dione (DNQX, 15 M; RBI), and MK-801 (40 Agmon, A., and Connors, B.W. (1992). Correlation between intrinsic M) were added to the perfusate. In some experiments, Ca 2ϩ was firing patterns and thalamocortical synaptic responses of neurons replaced by 4 mM [Sr] and [Mg] was raised to 4 mM, and the solution in mouse barrel cortex. J. Neurosci. 12, 319-329. was introduced at least 15 min before recording started. Ahmed, B., Anderson, J.C., Douglas, R.J., Martin, K.A.C., and Nelson, J.C. (1994). Polyneuronal innervation of spiny stellate neurons in cat visual cortex. J. Comp. Neurol. 341, 39-49. Minimal Stimulation Bear, M.F., and Malenka, R.C. (1994). Synaptic plasticity: LTP and During minimal-stimulation experiments, we used a bathing solution LTD. Curr. Opin. Neurobiol. 4, 389-399. containing 3 mM [Ca] and 1 mM [Mg]. To apply as focal a stimulus as possible, we developed a homemade stimulating electrode from Buhl, E.H., Tamas, G., Szilagyi, T., Stricker, C., Paulsen, O., and 2 mm outside diameter glass tubing with a cross section. The Somogyi, P. (1997). Effect, number and location of synapses made glass was pulled in a conventional two-stage puller to a tip size of by single pyramidal cells onto aspiny interneurones of cat visual Ͻ10 m in diameter. Each side of the tubing was filled with ACSF, cortex. J. Physiol. (Lond.) 500, 689-713. and electrical contact was made through two AgCl wires pushed Calverley, R.K.S., and Jones, D.G. (1990). Contribution of dendritic as close as possible to the tip. The tip was gently pushed into the spines and perforated synapses to synaptic plasticity. Brain Res. slice, and low stimulus intensities (Ͻ10 A, 0.1-0.2 ms duration) Rev. 15, 215-249. were used to minimize the area of activation; such stimuli always Castro-Alamancos, M.A., and Connors, B.W. (1996). Short-term failed to evoke a measurable field potential near the recorded cortiplasticity of a thalamocortical pathway dynamically modulated by cal neuron. The criteria for single-axon stimulation were: (1) all-orbehavioral state. Science 272, 274-277. none synaptic events, (2) little or no variation in EPSC latencies, (3) Castro-Alamancos, M.A., and Connors, B.W. (1997). Distinct forms a small change in the stimulus intensity did not change the mean of short-term plasticity at excitatory synapses of hippocampus and size or shape of the EPSC, and (4) lowering stimulus intensities by neocortex. Proc. Natl. Acad. Sci. USA 94, 4161-4166. 10%-20% resulted in complete failure to evoke EPSCs. Typically, 150-200 trials were obtained from each cell. Chance, F.S., Nelson, S.B., and Abbott, L.F. (1998). Synaptic depression and temporal response characteristics of V1 cells. J. Neurosci. 18, 4785-4799. Data Analysis Chung, S., and Ferster, D. (1998). Strength and orientation tuning Unitary EPSPs or EPSCs and spontaneous events were detected of the thalamic input to simple cells revealed by electrically evoked by threshold and by the first derivative (Malgaroli and Tsien, 1992; cortical suppression. Neuron 20, 1177-1189. Oliet et al., 1996) and were inspected by eye with software pro-Crair, M.C., and Malenka, R.C. (1995). A critical period for long-term grammed under the LabView environment (National Instruments). potentiation at thalamocortical synapses. Nature 375, 325-328. Baseline noise was measured during a 5 ms time window preceding Debanne, D., Guerineau, N.C., Gahwiler, B.H., and Thompson, S.M. each measured event. The signal-to-noise ratio for quantal EPSCs (1996). Paired-pulse facilitation and depression at unitary synapses was calculated as the ratio between the mean event amplitude and in rat hippocampus: quantal fluctuation affects subsequent release. the standard deviation of the noise, and was very similar for both J. Physiol. (Lond.) 491, 163-175. tracts (9.2 for the TC tract and 9.4 for the IC tract). Thus, there is no reason to suspect that we have missed a substantial number of Deuchars, J., West, D.C., and Thomson, A.M. (1995). Relationships events in either pathway or that events were differentially missed. between morphology and physiology of pyramid-pyramid single The progressive block of NMDA EPSCs in the presence of MKaxon connections in rat neocortex in vitro. J. Physiol. (Lond.) 478, 801 was fitted with a biexponential curve, using a simplex fitting 423-435. algorithm to minimize 2 (Kullmann et al., 1996). For analysis of Dobrunz, L.E., and Stevens, C.F. (1997). Heterogeneity of release EPSC/P amplitude distributions, a sum of Gaussian functions was probability, facilitation, and depletion at central synapses. Neuron fitted to the histograms by the method of least squares (Paulsen 18, 995-1008. and Heggelund, 1994). Statistical comparisons were made with the Dodge, F.A., Miledi, R., and Rahamimoff, R. (1969). Sr 2ϩ and quantal Wilcoxon test for paired samples, the Mann-Whitney test for unrelease of transmitter at the neuromuscular junction. J. Physiol. 200, paired samples, or t tests. The coefficient of variation (CV) was 267-284. defined as ( s 2 Ϫ n 2 ) 1/2 / s , where s and n are the variances of the Douglas, R.J., Koch, C., Mahowald, M., Martin, K.A.C., and Suarez, synaptic measurements and noise, respectively, and s is the mean H.H. (1995). Recurrent excitation in neocortical circuits. Science 269, synaptic size. The comparison between the TC and the IC cumula-981-985. tive distributions was made using the resampling (bootstrapping) Ferster, D., Chung, S., and Wheat, H. (1996). Orientation selectivity method (Van der Kloot, 1996). Unless specified, data are reported of thalamic input to simple cells of cat visual cortex. Nature 380, as mean Ϯ SD. 249-252. Fleidervish, I.A., Binshtok, A.M., and Gutnick, M.J. (1998). Function-
Neuron, 1999
connections from thalamus to cortex are significantly of each input to the construction of receptive field propmore effective than IC connections; although quantal erties in primary sensory areas of cortex is unclear. This size is the same in the two tracts, TC connections have issue has been intensively investigated for orientation a higher innervation ratio and release probability than selectivity in visual cortex. Some studies have con-IC connections. cluded that spatially aligned TC inputs alone account for orientation selectivity, while others suggest that recurrent IC circuits provide essential enhancement of Results weak TC inputs (for discussions, see Hubel and Wiesel, 1962; Douglas et al., 1995; Reid and Alonso, 1995, 1996; Our basic strategy was to record from single spiny neurons of the primary somatosensory (barrel) cortex in vitro and independently measure the properties of TC and IC inputs to each cell (Gil and Amitai, 1996; Gil et ‡ To whom correspondence should be addressed (e-mail: barry_ connors@brown.edu). al., 1997). The biocytin-stained cells we recovered (n ϭ Neuron 386 Gil and Amitai, 1996; Gil et al., 1997). Crossed paired pulses were References used to verify that stimuli of one tract were not contaminated by activation of axons from the other tract (Gil et al., 1997). In some Abdul-Ghani, M.A., Valiante, T.A., and Pennefather, P.S. (1996). Sr 2ϩ and quantal events at excitatory synapses between mouse hippo-experiments, biocytin (0.1%) was included in the pipette solution, and the slices were processed by standard avidin-biotin-peroxidase campal neurons in culture. J. Physiol. (Lond.) 495, 113-125. procedures (Horikawa and Armstrong, 1988). Agmon, A., and Connors, B.W. (1991). Thalamocortical responses The transmitter receptor blockers bicuculline methiodide (BMI, 5 of mouse somatosensory (barrel) cortex in vitro. Neuroscience 41, M; RBI), D,L-2-amino-5-phosphonovalerate (APV, 30 M; RBI), 6,7-365-379. dinitroquinoxaline-2,3-dione (DNQX, 15 M; RBI), and MK-801 (40 Agmon, A., and Connors, B.W. (1992). Correlation between intrinsic M) were added to the perfusate. In some experiments, Ca 2ϩ was firing patterns and thalamocortical synaptic responses of neurons replaced by 4 mM [Sr] and [Mg] was raised to 4 mM, and the solution in mouse barrel cortex. J. Neurosci. 12, 319-329. was introduced at least 15 min before recording started. Ahmed, B., Anderson, J.C., Douglas, R.J., Martin, K.A.C., and Nelson, J.C. (1994). Polyneuronal innervation of spiny stellate neurons in cat visual cortex. J. Comp. Neurol. 341, 39-49. Minimal Stimulation Bear, M.F., and Malenka, R.C. (1994). Synaptic plasticity: LTP and During minimal-stimulation experiments, we used a bathing solution LTD. Curr. Opin. Neurobiol. 4, 389-399. containing 3 mM [Ca] and 1 mM [Mg]. To apply as focal a stimulus as possible, we developed a homemade stimulating electrode from Buhl, E.H., Tamas, G., Szilagyi, T., Stricker, C., Paulsen, O., and 2 mm outside diameter glass tubing with a cross section. The Somogyi, P. (1997). Effect, number and location of synapses made glass was pulled in a conventional two-stage puller to a tip size of by single pyramidal cells onto aspiny interneurones of cat visual Ͻ10 m in diameter. Each side of the tubing was filled with ACSF, cortex. J. Physiol. (Lond.) 500, 689-713. and electrical contact was made through two AgCl wires pushed Calverley, R.K.S., and Jones, D.G. (1990). Contribution of dendritic as close as possible to the tip. The tip was gently pushed into the spines and perforated synapses to synaptic plasticity. Brain Res. slice, and low stimulus intensities (Ͻ10 A, 0.1-0.2 ms duration) Rev. 15, 215-249. were used to minimize the area of activation; such stimuli always Castro-Alamancos, M.A., and Connors, B.W. (1996). Short-term failed to evoke a measurable field potential near the recorded cortiplasticity of a thalamocortical pathway dynamically modulated by cal neuron. The criteria for single-axon stimulation were: (1) all-orbehavioral state. Science 272, 274-277. none synaptic events, (2) little or no variation in EPSC latencies, (3) Castro-Alamancos, M.A., and Connors, B.W. (1997). Distinct forms a small change in the stimulus intensity did not change the mean of short-term plasticity at excitatory synapses of hippocampus and size or shape of the EPSC, and (4) lowering stimulus intensities by neocortex. Proc. Natl. Acad. Sci. USA 94, 4161-4166. 10%-20% resulted in complete failure to evoke EPSCs. Typically, 150-200 trials were obtained from each cell. Chance, F.S., Nelson, S.B., and Abbott, L.F. (1998). Synaptic depression and temporal response characteristics of V1 cells. J. Neurosci. 18, 4785-4799. Data Analysis Chung, S., and Ferster, D. (1998). Strength and orientation tuning Unitary EPSPs or EPSCs and spontaneous events were detected of the thalamic input to simple cells revealed by electrically evoked by threshold and by the first derivative (Malgaroli and Tsien, 1992; cortical suppression. Neuron 20, 1177-1189. Oliet et al., 1996) and were inspected by eye with software pro-Crair, M.C., and Malenka, R.C. (1995). A critical period for long-term grammed under the LabView environment (National Instruments). potentiation at thalamocortical synapses. Nature 375, 325-328. Baseline noise was measured during a 5 ms time window preceding Debanne, D., Guerineau, N.C., Gahwiler, B.H., and Thompson, S.M. each measured event. The signal-to-noise ratio for quantal EPSCs (1996). Paired-pulse facilitation and depression at unitary synapses was calculated as the ratio between the mean event amplitude and in rat hippocampus: quantal fluctuation affects subsequent release. the standard deviation of the noise, and was very similar for both J. Physiol. (Lond.) 491, 163-175. tracts (9.2 for the TC tract and 9.4 for the IC tract). Thus, there is no reason to suspect that we have missed a substantial number of Deuchars, J., West, D.C., and Thomson, A.M. (1995). Relationships events in either pathway or that events were differentially missed. between morphology and physiology of pyramid-pyramid single The progressive block of NMDA EPSCs in the presence of MKaxon connections in rat neocortex in vitro. J. Physiol. (Lond.) 478, 801 was fitted with a biexponential curve, using a simplex fitting 423-435. algorithm to minimize 2 (Kullmann et al., 1996). For analysis of Dobrunz, L.E., and Stevens, C.F. (1997). Heterogeneity of release EPSC/P amplitude distributions, a sum of Gaussian functions was probability, facilitation, and depletion at central synapses. Neuron fitted to the histograms by the method of least squares (Paulsen 18, 995-1008. and Heggelund, 1994). Statistical comparisons were made with the Dodge, F.A., Miledi, R., and Rahamimoff, R. (1969). Sr 2ϩ and quantal Wilcoxon test for paired samples, the Mann-Whitney test for unrelease of transmitter at the neuromuscular junction. J. Physiol. 200, paired samples, or t tests. The coefficient of variation (CV) was 267-284. defined as ( s 2 Ϫ n 2 ) 1/2 / s , where s and n are the variances of the Douglas, R.J., Koch, C., Mahowald, M., Martin, K.A.C., and Suarez, synaptic measurements and noise, respectively, and s is the mean H.H. (1995). Recurrent excitation in neocortical circuits. Science 269, synaptic size. The comparison between the TC and the IC cumula-981-985. tive distributions was made using the resampling (bootstrapping) Ferster, D., Chung, S., and Wheat, H. (1996). Orientation selectivity method (Van der Kloot, 1996). Unless specified, data are reported of thalamic input to simple cells of cat visual cortex. Nature 380, as mean Ϯ SD. 249-252. Fleidervish, I.A., Binshtok, A.M., and Gutnick, M.J. (1998). Function-
Proceedings of the …, 2002
Electrical stimulation of the thalamus has been widely used to test for the existence of monosynaptic input to cortical neurons, typically with stimulation currents that evoke cortical spikes with high probability. We stimulated the lateral geniculate nucleus (LGN) of the thalamus and recorded monosynaptically evoked spikes from layer 4 neurons in visual cortex. We found that with moderate currents, cortical spikes were evoked with low to moderate probability and their occurrence was modulated by ongoing sensory (visual) input. Furthermore, when repeated at 8 -12 Hz, electrical stimulation of the thalamic afferents caused such profound inhibition that cortical spiking activity was suppressed, aside from electrically evoked monosynaptic spikes. Visual input to layer 4 cortical cells between electrical stimuli must therefore have derived exclusively from LGN afferents. We used white-noise visual stimuli to make a 2D map of the receptive field of each cortical simple cell during repetitive electrical stimulation in the LGN. The receptive field of electrically evoked monosynaptic spikes (and thus of the thalamic input alone) was significantly elongated. Its primary subfield was comparable to that of the control receptive field, but secondary (flanking) subfields were weaker. These findings extend previous results from intracellular recordings, but also demonstrate the effectiveness of an extracellular method of measuring subthreshold afferent input to cortex.