Corticostriatal and Thalamostriatal Synapses Have Distinctive Properties

Stimulus trains further differentiate corticostriatal and thalamostriatal synaptic plasticity. A, Whole-cell voltage-clamp recordings of EPSCs elicited by train stimulation (50 Hz, 5 pulses). EPSCs were fitted with five double-exponential functions (blue traces). B, Normalized EPSCs elicited by train stimulation. C, Each individual EPSC was generated and plotted based on fitted values. D, Fit EPSC amplitudes normalized to the first EPSC amplitude and plotted against stimulus number (50 Hz). Error bars indicate SEM. Asterisks indicate statistical significance.

Intrastriatal stimulation produces distinctive short-term plasticity in striatopallidal and striatonigral MSNs. A, Composite image of a sagittal slice and sagittal diagram of mouse brain showing cortex (Ctx), striatum (CPu), lateral globus pallidus (LGP), internal capsule (i.c.), corpus callosum (cc), lateral ventricle (LV), laterodorsal thalamus nucleus, ventrolateral part (LDVL), ventral posteromedial thalamic nucleus (VPM), ventral posterolateral thalamic nucleus (VPL), field CA3 of hippocampus (CA3), and forceps minor of the corpus callosum (fmi). The shaded area indicates the region where EPSCs can be reliably evoked by cortical stimulation in the striatum. B, Experimental configuration. Stim., Stimulation. C, EPSCs recorded in striatonigral (top) and striatopallidal (bottom) neurons elicited by paired stimuli with increasing ISIs with stimulation electrode placed in the cortex (cortical stimulation). D, Summary graph of PPRs elicited by cortical stimulation recorded in striatonigral neurons (black circle) and striatopallidal neurons (red circle) plotted against ISIs. PPRs are not significantly different between striatonigral and striatopallidal neurons. E, EPSCs recorded in striatonigral (top) and striatopallidal (bottom) neurons elicited by intrastriatal stimulation. The EPSCs were recorded from the same cells as shown in C. F, Summary graph of PPRs of intrastriatal stimulation from the same set of striatonigral neurons (black square) and striatopallidal neurons (red square) shown in D plotted versus ISIs. PPRs at short ISIs were significantly lower with intrastriatal stimulation in striatopallidal neurons compared with striatonigral neurons. Error bars indicate SEM. The asterisk indicates statistical significance.

CTZ does not significantly alter corticostriatal and thalamostriatal EPSCs PPRs. A, B, Thalamostriatal EPSCs elicited by paired stimuli with increasing ISIs in control condition and in the presence of CTZ. C, EPSCs (holding potential, −70 mV) with an ISI of 50 ms in control and CTZ. D, Box-plot summary of PPRs at an ISI of 50 ms. E, Summary graph of PPRs recorded from medium spiny neurons plotted against ISI for thalamic stimulation in control (triangles) and CTZ (filled triangles). F, G, Corticostriatal EPSCs elicited by paired stimuli in control condition and in the presence of CTZ. H, EPSCs (holding potential, −70 mV) with an ISI of 50 ms in control and CTZ. I, Box-plot summary of PPRs at an ISI of 50 ms. J, Summary graph of PPRs recorded from medium spiny neurons plotted against ISI for cortical stimulation in control (circle) and CTZ (filled circle). Error bars indicate SEM. The asterisk indicates statistical significance.

Sr²⁺-induced asynchronous release differs at corticostriatal and thalamostriatal synapses. A, B, Sample traces of EPSCs evoked by cortical (A) and thalamic (B) stimulation in the presence of 2 mm Ca²⁺ or 2 mm Sr²⁺/0 Ca²⁺. C, Box-plot summary of asynchronous release frequency. D, Box-plot summary showing no difference in qEPSC size at corticostriatal and thalamostriatal synapses. E, Amplitude histogram of AMPAR qEPSCs in 2 mm Sr²⁺/0 Ca²⁺ solution evoked by cortical and thalamic stimulation. F, Cumulative 10–90% rise and decay time distributions of AMPAR qEPSCs in 2 mm Sr²⁺/0 Ca²⁺ solution by cortical and thalamic stimulation. Black, Cortical stimulation; red, thalamic stimulation.The asterisk indicates statistical significance.The blue bars are the distribution of baseline amplitudes.

Altering external calcium concentration affects PPRs and synaptic variance, indicating a higher release probability at thalamostriatal synapses. A, Paired-pulse thalamic stimulation responses in 0.5 mm Ca²⁺/2.5 mm Mg²⁺, 2 mm Ca²⁺/1 mm Mg²⁺, and 4 mm Ca²⁺/0.5 mm Mg²⁺ external solutions. B, Normalized thalamostriatal EPSCs elicited by paired-pulse stimulation. C, Box-plot summary of thalamostriatal PPRs at ISI of 50 ms in different external calcium solutions. D, Paired-pulse cortical stimulation responses in the same recording conditions as in A. E, Normalized corticostriatal EPSCs elicited by paired-pulse stimulation. F, Box-plot summary of corticostriatal PPRs at ISI of 50 ms in different external calcium solutions. G, Plot of individual evoked EPSC amplitude for thalamic stimulation in different calcium/magnesium ratio external solution recording conditions (top) and individual evoked EPSC amplitude for cortical stimulation in the same recording conditions (bottom). H, Average variance–mean curve for thalamostriatal EPSCs (red circle; n = 7 cells) and corticostriatal EPSCs (open circle; n = 7 cells). Data points were fit with a parabola (see Materials and Methods). At 2 mm Ca²⁺/1 mm Mg²⁺, the estimated release probability was 0.72 for thalamostriatal synapses and 0.42 for corticostriatal synapses.Error bars indicate SEM. Asterisks indicate statistical significance.

Corticostriatal and thalamostriatal synapses differ in NMDA/AMPA ratio and NR2B/NMDA ratio. A, D, Representative traces demonstrating how NMDA, AMPA and NR2B traces were constructed. Total EPSC traces were elicited by cortical or thalamic stimulation while holding MSNs at +40 mV. B, Representative traces of NMDA and AMPA EPSCs elicited by cortical and thalamic stimulation. C, Box-plot summary of NMDA/AMPA ratios demonstrating a significantly smaller NMDA/AMPA ratio in corticostriatal synapses compared with thalamostriatal synapses. Corticostriatal and thalamostriatal NMDA/AMPA ratios were not significantly different between striatopallidal and striatonigral MSNs. E, Representative traces of NR2B and NMDA EPSCs elicited by cortical and thalamic stimulation. F, Box-plot summary of NR2B/NMDA ratios demonstrating significantly larger NR2B/NMDA ratios in thalamostriatal synapses compared with corticostriatal synapses. Corticostriatal and thalamostriatal NR2B/NMDA ratios were not significantly different between striatopallidal and striatonigral MSNs.Asterisks indicate statistical significance.