Short-Term Plasticity at Inhibitory Synapses in Rat Striatum and Its Effects on Striatal Output

Abstract

Two forms of short-term plasticity at inhibitory synapses were investigated in adult rat striatal brain slices using intracellular recordings. Intrastriatal stimulation in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM) and D,L-2-amino-5-phosphonovaleric acid (50 microM) produced an inhibitory postsynaptic potential (IPSP) that reversed polarity at -76 +/- 1 (SE) mV and was sensitive to bicuculline (30 microM). The IPSP rectified at hyperpolarized membrane potentials due in part to activation of K(+) channels. The IPSP exhibited two forms of short-term plasticity, paired-pulse depression (PPD) and synaptic augmentation. PPD lasted for several seconds and was greatest at interstimulus intervals (ISIs) of several hundred milliseconds, reducing the IPSP to 80 +/- 2% of its control amplitude at an ISI of 200 ms. Augmentation of the IPSP, elicited by a conditioning train of 15 stimuli applied at 20 Hz, was 119 +/- 1% of control when sampled 2 s after the conditioning train. Augmentation decayed with a time constant of 10 s. We tested if PPD and augmentation modify the ability of the IPSP to prevent the generation of action potentials. A train of action potentials triggered by a depolarizing current injection of constant amplitude could be interrupted by stimulation of an IPSP. If this IPSP was the second in a pair of IPSPs, it was less effective in blocking spikes due to PPD. By contrast, augmented IPSPs were more effective in blocking spikes. The same results were achieved when action potentials were triggered by a depolarizing current injection of varying amplitude, a manipulation that produces nearly identical spike times from trial to trial and approximates the in vivo behavior of these neurons. These results demonstrate that short-term plasticity of inhibition can modify the output of the striatum and thus may be an important component of information processing during behaviors that involve the striatum.

Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum

“…With this method, a presynaptic D 2 -mediated modulation similar to that shown on the striatopallidal pathway (Cooper and Stanford, 2001;Mengual and Pickel, 2002) or in the cholinergic or fastspiking (FS) interneurons (Pisani et al, 2000;Momiyama and Koga, 2001;Centonze et al, 2003) was shown. Similarly, a presynaptic modulation by D 1 receptor agonists as that reported in the striatonigral pathway (Floran et al, 1990(Floran et al, , 1997Cameron and Williams, 1993;Radnikow and Misgeld, 1998) was also shown, despite postsynaptic dopaminergic actions (Pacheco-Cano et al, 1996) on the subthreshold inward rectification Nisenbaum and Wilson, 1995;Mermelstein et al, 1998;Farries and Perkel, 2000) that shunts inhibitory inputs (Fitzpatrick et al, 2001).…”

“…A lack of consistency in the action of dopaminergic drugs on intrastriatally evoked inhibition, as recorded in spiny cells, has been reported previously (Delgado et al, 2000;Fitzpatrick et al, 2001) and probably results from a great variety of dopaminergic actions on a diverse array of GABAergic terminals and interneurons targeting spiny cells (Lenz et al, 1994;Pisani et al, 2000;Momiyama and Koga, 2001;Bracci et al, 2002;Yasumoto et al, 2002;Centonze et al, 2003;Gao et al, 2003). When none of these actions predominate over the others in most trials, inconsistent effects should be seen.…”

“…The latter responses are likely to be variable because they come from a mixed source of GABAergic terminals: several classes of interneurons and recurrent axon collaterals (Kita, 1993;Jaeger et al, 1994;Kawaguchi et al, 1995;Koos and Tepper, 1999;Fitzpatrick et al, 2001). In case all interneuron types do not respond in the same manner to different classes of dopamine receptor agonists (Aosaki et al, 1998;Bracci et al, 2002;Centonze et al, 2002Centonze et al, , 2003Yasumoto et al, 2002;Gao et al, 2003), it is expected that variety will make this mixed source inconsistent when responding to the agonists.…”

“…Otherwise, modulation would be concealed by the mixed source of differentially modulated inputs (Fitzpatrick et al, 2001). This work reports strong evidence of a selective role of dopamine in the presynaptic modulation of recurrent axon collaterals that interconnect spiny neurons.…”

Fast synaptic transmission between striatal spiny projection neurons

“…Second, synaptic augmentation (30) and paired-pulse depression (29,30) have also been described for GABAergic responses to extracellular shock stimulation in striatal projection neurons. Furthermore, prolonged PSP decay at high-burst frequencies and plateau-like depolarization during such bursts are reminiscent of asynchronous GABA release that was also described in dual recordings from unidentified striatal neurons in dissociated cultures (31).…”