6-cyano-7-nitroquinoxaline-2-3-dione and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphate

Application of the convulsant 4-aminopyridine (4AP, 50 microM) to adult mouse combined hippocampus-entorhinal cortex (EC) slices induces interictal and ictal discharges originating from CA3 and EC respectively. In this model of limbic seizures, ictal discharges disappear over time and are reestablished after Schaffer collateral cut, a procedure that blocks interictal propagation from CA3 to EC. Here we tested whether this form of network plasticity is operant in hippocampus-EC slices obtained from young (10-25 day-old) mice. In these experiments 4AP elicited interictal (duration = 100-250 ms; interval = 0.7 +/- 0.2 s, mean +/- SD, n = 20) and ictal (duration = 267 +/- 37 s; interval = 390 +/- 37 s, n = 20) discharges in both CA3 and EC. However, in young mouse slices the ictal events occurred throughout the experiment, whereas Schaffer collateral cut abolished CA3-driven interictal discharges in EC without influencing ictal activity (n = 10). Perforant path lesion prevented the spread of EC-driven ictal events to CA3, where interictal and short ictal discharges (duration = 32 +/- 11 s; interval = 92 +/- 9.7 s, n = 8) continued to occur. Hence, two independent forms of ictal activity were seen in CA3 and in EC after separation of these structures. In intact hippocampus-EC slices, ictal discharges were reduced by an N-methyl-D-aspartate receptor antagonist (n = 10). Under these conditions, Schaffer collateral cut abolished ictal activity in EC, not in CA3 (n = 6). Thus the young mouse hippocampus-EC loop has different properties as compared with adult tissue. These differences, which include the inability of hippocampal outputs to control ictal discharge generation in EC and the ability of the loop to sustain ictal activity, may contribute to the low-seizure threshold seen in young individuals.

Topics: 4-Aminopyridine; 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Entorhinal Cortex; Excitatory Amino Acid Antagonists; Hippocampus; In Vitro Techniques; Limbic System; Membrane Potentials; Mice; Mice, Inbred BALB C; Perforant Pathway; Piperazines; Receptors, N-Methyl-D-Aspartate; Seizures

Organotypic cocultures of dorsal root ganglia and spinal cord from embryonic rats provides direct access to spinal interneurons in a culture system in which the cytoarchitectural organization of the spinal cord slice is maintained. This preparation was used to investigate the possible induction of rhythmic behaviour at different times of development in vitro. Spontaneous rhythmic bursts induced by coapplication of strychnine (1 microM) and bicuculline (20 microM) were observed with patch-clamp recordings from ventral interneurons. Ventral horn interneurons consistently developed a very regular pattern of activity which was superimposed on a background of sustained synaptic activity. The pattern of the spontaneous bursting following application of strychnine and bicuculline showed a developmentally regulated difference in frequency between two distinct stages of in vitro development.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Bicuculline; Cells, Cultured; Coculture Techniques; Fetus; Gene Expression Regulation, Developmental; Membrane Potentials; Nerve Net; Neurons; Piperazines; Rats; Spinal Cord; Strychnine; Synaptic Transmission; Tetrodotoxin

In young rats, low frequency (1-2 Hz) stimulation of the Schaffer collaterals for 15 min induces in the CA1 area of the hippocampus a homosynaptic and N-methyl-D-aspartate receptor-dependent form of long-term depression (LTD) of synaptic efficacy. In the adults, while a similar stimulation paradigm is able to depress previously potentiated synapses, it leads to conflicting results when applied to naive synapses. In the present experiments, different stimulation paradigms have been used to induce LTD in the CA1 area of the adult rat hippocampus in vitro. Thus, stimulation of the afferent pathway at frequencies higher than those used to produce LTD in young animals (5-10 Hz, for 15 min) reliably induced a homosynaptic form of LTD. This form of LTD was associated with a significant increase in paired-pulse facilitation ratio and was insensitive to ionotropic (CNQX, 10 microM and CPP, 20 microM) and metabotropic (S-MCPG, 1 mM) glutamate receptors antagonists, suggesting a presynaptic mechanism for both LTD induction and expression. In conclusion, our experiments clearly show that LTD is not a purely developmental phenomenon but is present also in mature rats, which possess the whole machinery for LTD induction and this will greatly enhance the flexibility and the storing capacity of neuronal circuits.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Afferent Pathways; Animals; Culture Techniques; Electric Stimulation; Hippocampus; Microelectrodes; Piperazines; Rats; Rats, Wistar; Receptors, Glutamate; Receptors, Metabotropic Glutamate; Synapses; Synaptic Transmission; Time Factors

Synaptic physiology was studied in horizontal slices of rat somatosensory neocortex. Intrinsic properties of pyramidal neurons from horizontal slices resembled those recorded in cells from coronal slices, but cells in superficial horizontal slices displayed more prominent fast and slow inhibition, while cells from deeper slices showed disinhibition. This disinhibition in deeper horizontal slices resulted in epileptogenesis in 81% of middle and 35% of deep layer horizontal slices. Brief exposure to glutamate antagonists and dantrolene was ineffective in preventing epileptic activity, but limited pentobarbital exposure reduced the proportion of deep slices manifesting epileptiform activity by 75%. Thus, within cortex inhibition dominates superficially and excitation predominates in deeper layers. While the cortex is vulnerable to hyperexcitability when superficial cortex is compromised, enhancing fast inhibition can reset the excitation-inhibition balance, and prevent epileptogenesis.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Dantrolene; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA Modulators; In Vitro Techniques; Muscle Relaxants, Central; Neocortex; Neural Inhibition; Pentobarbital; Piperazines; Pyramidal Cells; Rats; Seizures; Somatosensory Cortex; Synapses

Evidence suggests that the prefrontal cortex (PFC) plays an important role in the burst activity of midbrain dopaminergic (DA) neurons. In particular, electrical stimulation of the PFC elicits patterns of activity in DA neurons, closely time-locked to the stimulation, which resemble natural bursts. Given that natural bursts are produced by the activity of excitatory amino acid (EAA)-ergic afferents, if PFC-induced time-locked bursts are homologues of natural bursts, EAA antagonists should attenuate them. Hence, the NMDA (N-methyl-D-aspartate) antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) and the AMPA (D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid)/kainate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) were applied by iontophoresis to DA neurons exhibiting time-locked bursts during PFC stimulation. CPP produced a significant reduction in time-locked bursting. In contrast, CNQX (at currents which antagonised AMPA responses) did not. These effects of CPP and CNQX on time-locked bursting mirror the effects previously reported for these drugs on natural bursting. Since natural bursting and bursting induced by PFC stimulation are both blocked selectively by CPP, the present results increase the degree of analogy between the two burst phenomena, thereby adding extra support to the contention that the cortex is involved in producing the natural bursting in DA neurons.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Binding, Competitive; Dopamine; Electric Stimulation; Excitatory Amino Acid Antagonists; Iontophoresis; Male; Neurons; Piperazines; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate; Respiratory Burst