Thalamocortical synaptic connections: efficacy, modulation, inhibition and plasticity (original) (raw)
Related papers
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-
Silent Synapses during Development of Thalamocortical Inputs
Neuron, 1997
94143 ous work, examined the occurrence of LTP at thalamocortical synapses in a slice preparation (Agmon and Connors, 1991), which contained the afferent connections from the ventrobasal nucleus Summary of the thalamus to layer IV cells in somatosensory (barrel) cortex. In slices prepared from early postnatal rats (P3-During development, activity-dependent mechanisms P7), robust, NMDA receptor-dependent LTP could be are thought to contribute to the refinement of topoelicited reliably. However, beginning at P8, LTP was graphical projections from the thalamus to the cortex.
2002
This study is concerned with the role of impulse activity and synaptic transmission in early thalamocortical development. Disruption of the gene encoding SNAP-25, a component of the soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor complex required for regulated neuroexocytosis, eliminates evoked but not spontaneous neurotransmitter release . The Snap25 null mutant mouse provides an opportunity to test whether synaptic activity is required for prenatal neural development. We found that evoked release is not needed for at least the gross formation of the embryonic forebrain, because the major features of the diencephalon and telencephalon were normal in the null mutant mouse. However, half of the homozygous mutants showed undulation of the cortical plate, which in the most severely affected brains was accompanied by a marked reduction of calbindin-immunoreactive neurons. Carbocyanine dye tracing of the thalamocortical fiber pathway revealed normal growth kinetics and fasciculation patterns between embryonic days 17.5 and 19. As in normal mice, mutant thalamocortical axons reach the cortex, accumulate below the cortical plate, and then start to extend side-branches in the subplate and deep cortical plate. Multiple carbocyanine dye placements in the cortical convexity revealed normal overall topography of both early thalamocortical and corticofugal projections. Electrophysiological recordings from thalamocortical slices confirmed that thalamic axons were capable of conducting action potentials to the cortex. Thus, our data suggest that axonal growth and early topographic arrangement of these fiber pathways do not rely on activity-dependent mechanisms requiring evoked neurotransmitter release. Intercellular communication mediated by constitutive secretion of transmitters or growth factors, however, might play a part.
Mechanisms Underlying the Early Establishment of Thalamocortical Connections in the Rat
The Journal of Neuroscience, 1998
We labeled axonal projections using carbocyanine dyes in the developing rat brain to study cellular interactions that might underlie the establishment of thalamocortical connectivity. By embryonic day 14 (E14), groups of neurons in the ventral diencephalon and the primitive internal capsule have established projections to the dorsal thalamus, and thalamic fibers pass in topographic order among them. Simultaneously, axons from the early-born cells in both subplate and marginal zone (i.e., the original cortical preplate) establish an ordered array that fills the intermediate zone. Thalamic axons and preplate fibers meet in the lateral part of the internal capsule (at E15 for occipital cortex and dorsolateral thalamus). Subsequently, selective labeling of corresponding thalamic and early corticofugal projections reveals thalamic fibers growing in association with early corticofugal axons, right up to the cortical subplate. A small carbocyanine crystal implanted at any point in the cortex shortly after the arrival of thalamic axons (E16 for the occipital cortex) labels a single, tight bundle containing both descending and ascending fibers, rather than two separate tracts, providing further evidence for intimate topographic association of the two axon systems. Crystals placed in a row, parasagittally or coronally along the hemisphere, reveal separate, topographically distributed, discrete fiber bundles throughout the pathway, leading to spatially ordered groups of back-labeled thalamic cells. These results indicate that the topography of thalamic axons is maintained throughout the pathway and that they reach the cortex by associating with the projections of a number of preexisting cells, including the preplate scaffold.
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-
Adult thalamocortical transmission involves both NMDA and non-NMDA receptors
Journal of neurophysiology, 1996
AND CONCLUSIONS 1. The involvement of N-methyl-D-aspartate (NMDA) receptors in thalamocortical transmission has been demonstrated in early postnatal development, but could not be determined so far in adult animals. We used thalamocortical slices from brains of mature mice to examine whether NMDA receptors exist in adult thalamocortical synapses, and what is their potential contribution to thalamocortical synaptic responses.
Synaptic patterns of thalamocortical afferents in mouse barrels at postnatal day 11
The Journal of Comparative Neurology, 2002
This study focuses on the synaptic output patterns of thalamocortical axons in mouse barrel cortex at postnatal day (P) 11. Axons were labeled by biotinylated dextran amine transported anterogradely following injection in vivo into the ventrobasal thalamus. Labeled axons in the posteromedial barrel subfield were examined by light and electron microscopy and then reconstructed in three dimensions to assess the spatial distribution of their synapses. Thalamocortical axons form asymmetrical synapses, both at varicosities and along cylindrical portions of the axons; usually, only one synapse occurs per site, contrasting with the case in the adult, in which multiple synapses are typical. At P11, varicosities without synapses are common. As in adult barrels, approximately 80% of synapses formed by thalamocortical axons are with dendritic spines; 20% are with dendritic shafts. The similarity in the distribution of thalamocortical synapses onto spines vs. dendrites in developing and mature barrels indicates that adult synaptic patterns already are specified at a very early stage of thalamocortical synaptogenesis.
Journal of Neuroscience, 2005
During the first week of life, there is a shift from kainate to AMPA receptor-mediated thalamocortical transmission in layer IV barrel cortex. However, the mechanisms underlying this change and the differential properties of AMPA and kainate receptor-mediated transmission remain essentially unexplored. To investigate this, we studied the quantal properties of AMPA and kainate receptor-mediated transmission using strontium-evoked miniature EPSCs. AMPA and kainate receptor-mediated transmission exhibited very different quantal properties but were never coactivated by a single quantum of transmitter, indicating complete segregation to different synapses within the thalamocortical input. Nonstationary fluctuation analysis showed that synaptic AMPA receptors exhibited a range of singlechannel conductance (␥) and a strong negative correlation between ␥ and functional channel number, indicating that these two parameters are reciprocally regulated at thalamocortical synapses. We obtained the first estimate of ␥ for synaptic kainate receptors (Ͻ2 pS), and this primarily accounted for the small quantal size of kainate receptor-mediated transmission. Developmentally, the quantal contribution to transmission of AMPA receptors increased and that of kainate receptors decreased. No changes in AMPA or kainate quantal amplitude or in AMPA receptor ␥ were observed, demonstrating that the developmental change was attributable to a decrease in the number of kainate synapses and an increase in the number of AMPA synapses contributing to transmission. Therefore, we demonstrate fundamental differences in the quantal properties for these two types of synapse. Thus, the developmental switch in transmission will dramatically alter information transfer at thalamocortical inputs to layer IV.
Nurturing the cortexʼs thalamic nature
Current Opinion in Neurology, 2014
Purpose of review Neocortical and thalamic interactions are necessary for the execution of complex sensory-motor tasks and associated cognitive processes. Investigation of thalamocortical circuit development is therefore critical to understand developmental disorders involving abnormal cortical function. Here, we review recent advances in our understanding of thalamus-dependent cortical patterning and cortical neuron differentiation. Recent findings Although the principles of cortical map patterning are increasingly understood, the extent to which thalamocortical inputs contribute to cortical neuron differentiation is still unclear. The recent development of genetic models allowing cell-type-specific dissection of cortical input pathways has shed light on some of the input-dependent and activity-dependent processes occurring during cortical development, which are discussed here. Summary These recent studies have revealed interwoven links between thalamic and cortical neurons, in which cell intrinsic differentiation programs are tightly regulated by synaptic input during a prolonged period of development. Challenges in the years to come will be to identify the mechanisms underlying the reciprocal interactions between intrinsic and extrinsic differentiation programs, and their contribution to neurodevelopmental disorders and neuropsychiatric disorders at large.
Alterations in the properties of neonatal thalamocortical synapses with time in in vitro slices
PLOS ONE, 2017
New synapses are constantly being generated and lost in the living brain with only a subset of these being stabilized to form an enduring component of neuronal circuitry. The properties of synaptic transmission have primarily been established in a variety of in vitro neuronal preparations. It is not clear, however, if newly-formed and persistent synapses contribute to the results of these studies consistently throughout the lifespan of these preparations. In neonatal somatosensory, barrel, cortex we have previously hypothesized that a population of thalamocortical synapses displaying unusually slow kinetics represent newly-formed, default-transient synapses. This clear phenotype would provide an ideal tool to investigate if such newly formed synapses consistently contribute to synaptic transmission throughout a normal experimental protocol. We show that the proportion of synapses recorded in vitro displaying slow kinetics decreases with time after brain slice preparation. However, slow synapses persist in vitro in the presence of either minocycline, an inhibitor of microglia-mediated synapse elimination, or the TrkB agonist 7,8-dihydroxyflavone a promoter of synapse formation. These findings show that the observed properties of synaptic transmission may systematically change with time in vitro in a standard brain slice preparation.