RESUMO
Medium spiny projection neurons (MSNs) are the main neuronal population in the neostriatum. MSNs are inhibitory and GABAergic. MSNs connect with other MSNs via local axon collaterals that produce lateral inhibition, which is thought to select cell assemblies for motor action. MSNs also receive inhibitory inputs from GABAergic local interneurons. This work shows, through the use of the paired pulse protocol, that somatostatin (SST) acts presynaptically to regulate GABA release from the terminals interconnecting MSNs. This SST action is reversible and not mediated through the release of dopamine. It is blocked by the SST receptor (SSTR) antagonist ciclosomatostatin (cicloSST). In contrast, SST does not regulate inhibition coming from interneurons. Because, SST is released by a class of local interneuron, it is concluded that this neuron helps to regulate the selection of motor acts.
Assuntos
Corpo Estriado/metabolismo , Potenciais Pós-Sinápticos Inibidores/fisiologia , Neurônios/metabolismo , Terminações Pré-Sinápticas/metabolismo , Somatostatina/metabolismo , 6-Ciano-7-nitroquinoxalina-2,3-diona/metabolismo , Potenciais de Ação/fisiologia , Animais , Corpo Estriado/citologia , Agonistas de Aminoácidos Excitatórios/metabolismo , Antagonistas de Aminoácidos Excitatórios/metabolismo , N-Metilaspartato/metabolismo , Neurônios/citologia , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Valina/análogos & derivados , Valina/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismoRESUMO
This work investigated if diverse properties could be ascribed to evoked inhibitory postsynaptic currents (IPSCs) recorded on rat neostriatal neurons when field stimulation was delivered at two different locations: the globus pallidus (GP) and the neostriatum (NS). Previous work stated that stimulation in the GP could antidromically excite projection axons from medium spiny neurons. This maneuver would predominantly activate the inhibitory synapses that interconnect spiny cells. In contrast, intrastriatal stimulation would preferentially activate inhibitory synapses provided by interneurons. This study shows that, in fact, intensity-amplitude experiments are able to reveal different properties for IPSCs evoked from these two locations (GP and NS). In addition, while all IPSCs evoked from the GP were always sensitive to omega-conotoxin GVIA (Ca(V2.2)2.2 or N-channel blocker), one-half of the inhibition evoked from the NS exhibited little sensitivity to omega-conotoxin GVIA. Characteristically, all omega-conotoxin GVIA-insensitive IPSCs exhibited strong paired pulse depression, whereas omega-conotoxin GVIA-sensitive IPSCs evoked from either the GP or the NS could exhibit short-time depression or facilitation. omega-Agatoxin TK (Ca(V2.1)2.1+ or P/Q-channel blocker) blocked IPSCs evoked from both locations. Therefore 1) distinct inhibitory inputs onto projection neostriatal cells can be differentially stimulated with field electrodes; 2) N-type Ca2+ channels are not equally expressed in inhibitory terminals activated in the NS; and 3) synapses that interconnect spiny neurons use both N- and P/Q-type Ca2+ channels.
Assuntos
Neostriado/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Animais , Estimulação Elétrica/métodos , Feminino , Técnicas In Vitro , Masculino , Vias Neurais/fisiologia , Ratos , Ratos WistarRESUMO
Besides a reduction of L-type Ca2+-currents (Ca(V)1), muscarine and the peptidic M1-selective agonist, MT-1, reduced currents through Ca(V)2.1 (P/Q) and Ca(V)2.2 (N) Ca2+ channel types. This modulation was strongly blocked by the peptide MT-7, a specific muscarinic M1-type receptor antagonist but not significantly reduced by the peptide MT-3, a specific muscarinic M4-type receptor antagonist. Accordingly, MT-7, but not MT-3, blocked a muscarinic reduction of the afterhyperpolarizing potential (AHP) and decreased the GABAergic inhibitory postsynaptic currents (IPSCs) produced by axon collaterals that interconnect spiny neurons. Both these functions are known to be dependent on P/Q and N types Ca2+ channels. The action on the AHP had an important effect in increasing firing frequency. The action on the IPSCs was shown to be caused presynaptically as it coursed with an increase in the paired-pulse ratio. These results show: first, that muscarinic M1-type receptor activation is the main cholinergic mechanism that modulates Ca2+ entry through voltage-dependent Ca2+ channels in spiny neurons. Second, this muscarinic modulation produces a postsynaptic facilitation of discharge together with a presynaptic inhibition of the GABAergic control mediated by axon collaterals. Together, both effects would tend to recruit more spiny neurons for the same task.
Assuntos
Acetilcolina/metabolismo , Caveolinas/fisiologia , Neostriado/citologia , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Caveolina 2 , Caveolinas/classificação , Caveolinas/efeitos dos fármacos , Células Cultivadas , Interações Medicamentosas , Estimulação Elétrica/métodos , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Muscarina/farmacologia , Agonistas Muscarínicos/classificação , Agonistas Muscarínicos/farmacologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp/métodos , Ratos , Ratos Wistar , Receptores Muscarínicos/classificação , Receptores Muscarínicos/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacosRESUMO
Dopamine is a critical modulator of striatal function; its absence produces Parkinson's disease. Most cellular actions of dopamine are still unknown. This work describes the presynaptic actions of dopaminergic receptor agonists on GABAergic transmission between neostriatal projection neurons. Axon collaterals interconnect projection neurons, the main axons of which project to other basal ganglia nuclei. Most if not all of these projecting axons pass through the globus pallidus. Thus, we lesioned the intrinsic neurons of the globus pallidus and stimulated neostriatal efferent axons antidromically with a bipolar electrode located in this nucleus. This maneuver revealed a bicuculline-sensitive synaptic current while recording in spiny cells. D1 receptor agonists facilitated whereas D2 receptor agonists depressed this synaptic current. In contrast, a bicuculline-sensitive synaptic current evoked by field stimulation inside the neostriatum was not consistently modulated, in agreement with previous studies. The data are discussed in light of the most recent experimental and modeling results. The conclusion was that inhibition of spiny cells by axon collaterals of other spiny cells is quantitatively important; however, to be functionally important, this inhibition might be conditioned to the synchronized firing of spiny neurons. Finally, dopamine exerts a potentially important role regulating the extent of lateral inhibition.