Intensity-dependent, rapid activation of presynaptic metabotropic glutamate receptors at a central synapse.

Synaptic signals from retinal bipolar cells were monitored by measuring EPSCs in ganglion cells voltage-clamped at -70 mV. Spontaneous EPSCs were strongly suppressed by l-2-amino-4-phosphonobutyrate (AP-4), an agonist at group III metabotropic glutamate receptors (mGluRs). Agonists of group I or II mGluRs were ineffective. AP-4 also suppressed ganglion cell EPSCs evoked by bipolar cell stimulation using potassium puffs, sucrose puffs, or zaps of current (0.5-1 microA). In addition, AP-4 suppressed Off EPSCs evoked by dim-light stimuli. This indicates that group III mGluRs mediate a direct suppression of bipolar cell transmitter release. An mGluR antagonist, (RS)-alpha-cyclopropyl-4-phosphonophenylyglycine (CPPG), blocked the action of AP-4. When bipolar cells were weakly stimulated, AP-4 produced a large suppression of the EPSC, but CPPG alone had little effect. Conversely, when bipolar cells were strongly stimulated, CPPG produced an enhancement of the EPSC, but AP-4 alone had little effect. This indicates that endogenous feedback regulates bipolar cell transmitter release and that the dynamic range of the presynaptic metabotropic autoreceptor is similar to that of the postsynaptic ionotropic receptor. Furthermore, the feedback is rapid and intensity-dependent. Hence, concomitant activation of presynaptic and postsynaptic glutamate receptors shapes the responses of ganglion cells.

Adolescent development alters stressor-induced Fos immunoreactivity in rat brain.

Adult-typical behavioural responses to environmental challenges as well as the stressor responsiveness of several neural systems emerge over adolescent development. The present study was undertaken to determine whether stressors might activate different neural populations in adult vs juvenile male rats. Fos-immunoreactivity was determined in various forebrain nuclei following 15 min or 2 h of restraint in 28- and 60-day-old male rats (representing late juvenile and young adult ages, respectively) and compared to non-restrained control animals at each age. Few Fos-positive cells were identified in unrestrained controls at either age. Restraint, however, induced the production of Fos in several areas. Fos immunoreactivity was marked in parvocellular regions of the paraventricular nucleus of the hypothalamus following both restraint periods and at both ages, an observation consistent with previous observations that restraint increases plasma corticosterone at both ages. And at both ages, Fos immunoreactivity was evident in magnocellular regions of the hypothalamus only following the longer restraint period. Fos immunoreactivity, however, clearly varied as a function of adolescent age in several regions. Moderate to intense Fos immunoreactivity was observed in adults in all divisions of the anterior olfactory nucleus, cortical and medial amygdaloid nuclei, pyriform cortex and tenia tecta. In contrast to the adult, only a few Fos positive cells were observed in any of these regions in juveniles. Exposure to the same stressor induced Fos in a broader spectrum of neurons in young adult than in juvenile male rats. The lack of Fos-positive cells in specific areas of juveniles may relate to maturation in specific amygdaloid nuclei, which project to many of the other regions that showed age-related differences in Fos production. The emergence over adolescence of Fos-positive cells in specific areas in response to stressors may underlie the emergence of adult-typical behavioural and neural stressor-responsiveness.

Effective release rates at single rat Schaffer collateral-CA1 synapses during sustained theta-burst activity revealed by optical imaging.

To understand how information is coded at single hippocampal synapses during high-frequency activity, we imaged NMDA receptor-mediated Ca(2+) responses in spines of CA1 neurons using two-photon microscopy. Although discrete quantal events were not readily apparent during continuous theta-burst stimulation (TBS), we found that the steady-state dendritic Ca(2+) response was spatially restricted (half-width < 1 microm), voltage dependent and sensitive to MK-801, indicating that that it was mediated by activation of NMDA receptors at single synapses. Partial antagonism of NMDA receptors caused a similar reduction of NMDA EPSCs (measured at the soma) and local dendritic Ca(2+) signals, suggesting that, like EPSCs, the steady-state Ca(2+) signal was made up of a linear addition of quantal events. Statistical analyses of the steady-response suggested that the quantal size did not change dramatically during TBS. Deconvolution of TBS-evoked Ca(2+) responses revealed a heterogeneous population of synapses differing in their capacity to signal high-frequency information, with an average effective steady-state release rate of approximately 2.6 vesicles synapse(-1)s(-1). To assess how the optically determined release rates compare with population measures we analysed the rate of decay of peak EPSCs during train stimulation. From these studies, we estimated a unitary vesicular replenishment rate of 0.02 s(-1), which corresponds to an average release rate of approximately 0.8-2 vesicles s(-1) at individual synapses. Additionally, extracellular recordings from single Schaffer collaterals revealed that spikes propagate reliably during TBS. Hence, during high-frequency activity, Schaffer collaterals conduct spikes with high fidelity, but release quanta with relatively lower efficiency, leaving NMDA receptor function largely intact and synapse specific. Heterogeneity in release rates between synapses suggests that similar patterns of presynaptic action potentials could trigger different forms of plasticity at individual synapses.

Origin of transient and sustained responses in ganglion cells of the retina.

Phasic and tonic light responses provide a fundamental division of visual information that is thought to originate in the inner retina. However, evidence presented here indicates that this duality originates in the outer retina. In response to a steady light stimulus, the temporal responses of On-bipolar cells fell into two groups. In one group, the light response peaked and then rapidly declined (tau approximately 400 msec) close to the resting membrane potential. At light offset, these cells exhibited a transient afterhyperpolarization. In the second group of On-bipolar cells, the light response declined 10-fold more slowly and reached a steady depolarization that was approximately 40% of the peak response. These neurons had a slowly decaying afterhyperpolarization at light offset. A metabotropic glutamate antagonist, (RS)-alpha-cyclopropyl-4-phosphonophenylyglycine (CPPG), blocked light responses in both types of On-bipolar cell. CPPG only slightly depolarized transient On-bipolar cells, whereas sustained On-bipolar cells were significantly depolarized. Inorganic calcium channel blockers disclosed that these distinct On-bipolar responses were inherent to the bipolar cell and not attributable to synaptic feedback. CPPG had distinct effects on sustained and transient ganglion cells, similar to its action on bipolar cells. The antagonist depolarized and blocked the light responses of sustained ganglion cells. In transient ganglion cells, CPPG suppressed the On light response but did not depolarize the cell or block the Off light response. These results suggest that transient and sustained light responses in ganglion cells result from selective bipolar cell input and that these two fundamental visual channels originate at the dendritic terminals of bipolar cells.