Non‐cholinergic synaptic excitation in neostriatum: pharmacological evidence for mediation by a glutamate‐like transmitter

Abstract

We studied the synaptic pharmacology of an excitatory pathway in the neostriatum using electrophysiological techniques in tissue slices from rats. In response to single electrical stimuli, two negative, extracellular potentials (N‐1 and N‐2) were recorded through micropipette electrodes within 150–450 μm of the stimulating cathode. N‐2 was reversibly reduced or abolished by reducing the concentration of calcium in the bathing medium, while N‐1 was unaffected. Both N‐1 and N‐2 were reversibly abolished by the local anaesthetic procaine. Single‐unit, extracellular action potentials were, at times, associated with either N‐1 or N‐2. Intracellular recordings showed action potentials at N‐2 latency arising from graded, monophasic, depolarizing potentials. Bath‐applied cholinoceptor and dopamine receptor antagonists failed to reduce N‐2. By contrast, antagonists of excitatory amino acid transmitters reversibly reduced or abolished N‐2. γ‐d‐Glutamylglycine (GG), (±)‐cis‐2,3‐piperidine dicarboxylic acid (PDA) and dL‐2‐amino‐4‐phosphonobutyric acid (APB) blocked N‐2 with ED50s of 0.79 mm, 1.0 mm and 1.1 mm, respectively. (−)−Baclofen reversibly blocked N‐2 with an ED50 of 0.79 μm; (+)‐baclofen was 330 times less potent. The results suggest that N‐1 results from direct activation of fibre tracts or cell bodies, while N‐2 is a population spike mediated by excitatory synapses whose natural transmitter pharmacologically resembles glutamate.

Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro

“…This observation is in agreement with the slow rise time of NMDA receptormediated activity recorded in cultured neurons from the hippocampus and the spinal cord (Forsythe and Westbrook 1988). Since low-affinity glutamate receptor antagonists were used in previous studies on synaptic responses in the ventral and dorsal striatum (Cordingley and Weight 1986;Cherubini et al 1988;Uchimura et al 1989b;Walsh et al 1989), the present investigations are the first to suggest that fast EPSPs evoked by local or callosal stimulation are almost completely mediated by Q/K receptors.…”

N‐type calcium channels mediate a GABAB presynaptic modulation in the corticostriatal synapse in turtle's paleostriatum augmentatum

“…The field potential amplitudes were insensitive to NMDA antagonists, they were: 58.67 6 10.65 lV before and 55.41 6 9.44 lV after AP-V (50 lM; n 5 9; not shown). Taken together our data suggest the presence of glutamatergic synapses with AMPA/kainate postsynaptic receptors alike to that observed in mammals (Barral et al, 2001;Cordingley and Weight, 1986;Fowler et al, 1999;Malenka and Kocsis, 1988;Miljanich and Ramachandran, 1995;Misgeld et al, 1979;Takagi and Yamamoto, 1978;Yamamoto, 1973) as suggested previously by immunocytochemical techniques in turtles (Fowler et al, 1999).…”

Norepinephrine Modulates Glutamatergic Transmission in the Bed Nucleus of the Stria Terminalis

“…Both peaks can be blocked using the Na þ channel blocker tetrodotoxin (TTX, 1 mM) (Figure 2b), suggesting that the first peak is due to axonal AP firing. These two peaks have been designated as N1 (the first negative peak) and N2 (the second negative peak) based on terminology from the striatal field potential literature (Cordingley and Weight, 1986;Malenka and Kocsis, 1988;Takagi and Yamamoto, 1978). Given the latency of the response and pharmacology indicating that the N2 peak is driven by glutamatergic receptor activation, the peak amplitude of the N2 was measured as an extracellular estimate of postsynaptic responses driven by excitatory glutamatergic synaptic transmission.…”