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Long-Term Synaptic Depression in the Striatum: Physiological and Pharmacological Characterization

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Long-Term Synaptic Depression in the Striatum: Physiological and Pharmacological Characterization The Journal of Neuroscience, November 1992, 12(11): 4224-4233 Long-Term Synaptic Depression in the Striatum: Physiological and Pharmacological Characterization Paolo Calabresi,1s2 Roberto Maj,’ Antonio Pisani,’ Nicola B. Mercuri,’ and Giorgio Bernardi’** ‘Clinica Neurologica, Dip. Sanit& II UniversitA di Roma, 00173 Rome, Italy and *lRCCS, Clinica S. Lucia, 00173 Rome, Italy The effect of tetanic activation of corticostriatal glutama- striatum to the other structures of the basal ganglia. This tergic fibers was studied in striatal slices by utilizing extra- form of synaptic plasticity can influence the striate1 control cellular and intracellular recording techniques. Tetanic stim- of motor activity. ulation produced a long-term synaptic depression (LTD) (>2 h) of both extracellularly recorded field potentials and intra- Use-dependent changes in synaptic efficacy have been widely cellularly recorded EPSPs. LTD was not coupled with changes studied in several neuronal systemsin order to investigate the of intrinsic membrane properties of the recorded neurons. possiblebiochemical and biophysical mechanismsthat underlie In some neurons, repetitive cortical activation produced a memory and learning. Repetitive stimulation of excitatory path- short-term posttetanic potentiation (1-3 min). Subthreshold ways in the brain results either in a persistent enhancementor tetanic stimulation, which under control condition did not in a permanent decreaseof synaptic transmission.These changes cause LTD, induced LTD when associated with membrane have been termed long-term potentiation (LTP) (Kuba and Ku- depolarization. Moreover, LTD was not expressed in cells in mamoto, 1990) and long-term depression (LTD) (Ito, 1989). which the conditioning tetanus was coupled with hyperpo- Since the hippocampus has been involved in processessuch as larization of the membrane. Bath application of aminophos- learning and memory (Scoville and Milner, 1957; Green, 1964; phonovalerate (30-50 PM), an antagonist of NMDA receptors, Colemann and Lindsley, 1977;Teyler and Discenna, 1984),dif- did not affect the amplitude of the synaptic potentials and ferent authors have hypothesized that LTP in the hippocampus the expression of LTD. Striatal LTD was significantly reduced (Blissand Lomo, 1973; Schwartzkroin and Wester, 1975; Morris by the pretreatment of the slices with 30 PM 2-amino-3-phos- et al., 1986) can represent the neural basis of some forms of phonopropionic acid, an antagonist of glutamate metabo- memory. It has also been reported that in the hippocampal field tropic receptors. LTD was not blocked by bicuculline (30 PM), CA1 , LTD can be produced when a low-frequency test input is a GABA, receptor antagonist. Scopolamine (3 FM), an an- negatively correlated in time with a high-frequency conditioning tagonist of muscarinic receptors, induced a slight, but sig- input (Stanton and Sejnowski, 1989). In visual cortex, where nificant, increase of the amplitude of LTD. Both SCH 23390 long-term changesof synaptic transmission have been impli- (3 PM), an antagonist of Dl dopamine (DA) receptors, and cated in developmental plasticity (Artola and Singer, 1987) Csulpiride (1 PM), an antagonist of D2 DA receptors, blocked tetanic stimulation of excitatory pathways can induce either LTD. LTD was also absent in slices obtained from rats in LTP or LTD depending on the level of depolarization of the which the nigrostriatal DA system was lesioned by unilateral postsynaptic neuron (Artola et al., 1990). Furthermore, models nigral injection of 6-hydroxydopamine. In DA-depleted slic- of cerebellar network functions have suggestedthat the parallel es, LTD could be restored by applying exogenous DA (30 fiber-Purkinje neuron synapse could be modifiable as a con- PM) before the conditioning tetanus. In DA-depleted slices, sequenceof climbing fiber activation (Marr, 1969; Albus, 1971). LTD could also be restored by coadministration of SKF 36393 This property was first observed in the intact cerebellumas LTD (3-10 PM), a Dl receptor agonist, and of LY 171555 (l-3 of synaptic transmission between parallel fibers and Purkinje pm), a D2 receptor agonist. Application of a single class of neurons following conjunctive stimulation of parallel fiber and DA receptor agonists failed to restore LTD. These data show climbing fiber inputs to Purkinje neurons (Ito et al., 1982; Kano that striatal LTD requires three main physiological and phar- and Kato, 1987, 1988). This phenomenon is now consideredto macological conditions: (1) membrane depolarization and be the basisof several forms of motor learning (Ito, 1989). More action potential discharge of the postsynaptic cell during the recently, cerebellar LTD has been demonstrated in slice (Sak- conditioning tetanus, (2) activation of glutamate metabo- urai, 1987; Crepe1and Krupa, 1988) and in tissueculture (Hir- tropic receptors, and (3) coactivation of Dl and D2 DA re- ano and Hagiwara, 1988). It has been recently confirmed, by ceptors. Striatal LTD may alter the output signals from the utilizing positron emissiontomography in humans (Seitz et al., 1990) that not only the cerebellum but also the basal ganglia Received Mar. 19, 1992; revised May 28, 1992; accepted May 29, 1992. are strongly involved in the storageof motor skills in the brain. We thank Dr. G. Sancesario for the immunohistochemical controls and Mr. G. In particular, the corticostriatal projection seemsto play a major Gattoni and Mr. M. Tolu for their excellent technical assistance. We also thank Dr. R. Fariello and Dr. M. Buonamici (Farm&ha) for providing lesioned animals role in motor learning (Seitz et al., 1990). This pathway utilizes and for measuring turning behavior. This study was supported by CNR grants to glutamate as a transmitter, and it is the main excitatory input P.C. Correspondence should be addressed to Dr. Paolo Calabresi, Clinica Neurologi- to the striatum (Spencer, 1976; Reubi and Cuenod, 1979).The ca, Dip. San&, II UniversitA di Roma, Via 0. Raimondo, 00173 Rome, Italy. physiology and the pharmacology of the glutamatergic corti- Copyright 0 1992 Society for Neuroscience 0270-6474/92/124224-10$05.00/O costriatal projection have beenwidely studiedboth in viva (Kitai The Journal of Neuroscience, November 1992, fZ(11) 4225 Table 1. Intrinsic membrane properties of striatal neurons measured before and after (10 min) tetanic stimulation of corticostriatal fibers Pretetanus Posttetanus Membrane potential (mV) n = 30 -85 k 6 -86 * 7 Input resistance (Ma) n = 20 46+ 13 48 k 12 Action potential amplitude (mV) n = 25 91&9 93t 11 Action potential duration (msec) n = 15 1.1 t 0.3 1.1 + 0.3 et al., 1976; Bishop et al., 1982; Herrling, 1985; Calabresi et and I-sulpiride were applied 15-20 min before the conditioning tetanus. al., 1990b, Wilson et al., 1990) and in vitro (Kita et al., 1984; In DA-depleted slices, within the first 5 min of application, DA and LY 17 1555 produced a decrease of the synaptic potentials (Calabresi et Calabresiet al., 1987a,b, 1988a,b, 1990~;Cherubini et al., 1988; al., 1988a,b) and we had to increase the intensity of stimulation to obtain Kawaguchi et al., 1989). Some recent evidence (Garcia-Munoz potentials of the same amplitude as those in the control medium. et al., 1991; Walsh, 1991) suggeststhat, under different condi- Dopamine-depleting procedures and determination of the lesion of the tions, long-term changes of corticostriatal synaptic transmission dopaminergicsystem. To obtain unilateral nigrostriatal lesions, rats were injected with 6-hydroxydopamine (6-OHDA, 8 &4 pl of saline con- can be observed. However, at present, the effect of repetitive taining 0.1% ascorbic acid) via a Hamilton syringe through a cannula activation of corticostriatal glutamatergic pathway has not yet inserted just rostra1 to the substantia nigra under stereotaxic coordinates been fully investigated. Thus, we have studied whether tetanic (Paxinos and Watson, 1986): A, 3.7 mm anterior to the interaural line; stimulation of corticostriatal fibers induces long-term changes V, 2.2 mm dorsal to the interaural line; L, 2.2 mm from the midline. of striatal synaptic transmission. In addition, we have tried to Twenty days later, the rats were tested with 0.5 mg/kg (s.c.) apomorphine and the contralateral turns were recorded with automatic rotometers characterize the physiological and the pharmacological mech- for 3 hr. Only those rats consistently making at least 200 contralateral anisms underlying possible long-term changes of synaptic trans- turns were used for the electrophysiological studies. After brain dissec- mission. tion, we confirmed that the nigrostriatal pathway was lesioned. This was established by noting a greater than 95% loss of DA neurons in the Materials and Methods substantia nigra compacta and the almost complete absence of DA terminals in the striatum. This was detected by an immunoperoxidase Preparation and maintenance of the slices. Male Wistar rats, weighing technique, which utilized a monoclonal antibody for tyrosine hydrox- 150-200 gm, were used for the experiments. The preparation and main- ylase. tenance of the slices have been described previously (Calabresi et al., 1987a, 1988a, 199Oc, 199 1). Briefly, coronal slices (200-300 pm) were prepared from tissue blocks of the brain with the use of a vibratome. Results These coronal slices included the neostriatum and neocortex. A single General characteristics of the recorded neurons slice was transferred to a recording chamber (vol, 0.5 ml) and submerged in a continuously flowing Krebs’ solution (36°C 2-3 ml/min) gassed These results are based on intracellular recordings from 101 with 95% O,, Soi0 CO, mixture. The composition of the solution was striatal neurons, recorded from slicesobtained from naive rats, (in mM) 126 NaCl. 2.5 KCl. 1.2 NaH,PO,._ II 1.2 MaCl,.1 _I 2.4 CaCl,.-I 11 and 32 cells, recorded from DA-depleted slices. In addition, glucose: and 25 NaHCO,. ’ extracellular experiments were performed on 78 slicesobtained Technique of recordings and stimulation parameters. Intracellular re- from naive rats and on 44 slices obtained from DA-lesioned cording electrodes were filled with 2 M KC1 (30-60 Mfi), while extra- cellular electrodes were filled with 2 M NaCl (S-10 MQ).
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