Orientation adaptation and perceptual learning change orientation tuning curves of V1 cells. Adaptation shifts tuning curve peaks away from the adapted orientation, reduces tuning curve slopes near the adapted orientation, and increases the responses on the far flank of tuning curves. Learning an orientation discrimination task increases tuning curve slopes near the trained orientation. These changes have been explained previously in a recurrent model (RM) of orientation selectivity. However, the RM generates only complex cells when they are well tuned, so that there is currently no model of orientation plasticity for simple cells. In addition, some feedforward models, such as the modified feedforward model (MFM), also contain recurrent cortical excitation, and it is unknown whether they can explain plasticity. Here, we compare plasticity in the MFM, which simulates simple cells, and a recent modification of the RM (MRM), which displays a continuum of simple-to-complex characteristics. Both pre- and postsynaptic-based modifications of the recurrent and feedforward connections in the models are investigated. The MRM can account for all the learning- and adaptation-induced plasticity, for both simple and complex cells, while the MFM cannot. The key features from the MRM required for explaining plasticity are broadly tuned feedforward inputs and sharpening by a Mexican hat intracortical interaction profile. The mere presence of recurrent cortical interactions in feedforward models like the MFM is insufficient; such models have more rigid tuning curves. We predict that the plastic properties must be absent for cells whose orientation tuning arises from a feedforward mechanism.

The developing cerebral cortex is likely to exhibit synaptic circuitries differing from those in adulthood, due to the asynchronous maturation of the various neurotransmitter systems. Two antisera directed against mammalian β-adrenergic receptors (βAR), βAR248 and βAR404, were used to characterize the laminar, cellular, and subcellular distributions of βAR in postnatally developing visual cortex of rats. The antigenic sites were the receptor's third intracellular loop for βAR248 and the C-terminus for βAR404. During week 1, most of the βAR404- and βAR248-immunoreactive sites were dendritic. Morphologically identifiable synapses were rare, even in layer 1: yet, semiquantitative analysis revealed that βAR404-immunoreactive synapses comprise half of those in layer 1. During week 2, the two antisera began to diverge in their immunoreactivity patterns. With βAR248, there was an overall decline in immunoreactivity, while with βAR404, there was an increase in immunoreactive sites, primarily due to labeled astrocytic processes that increased 200-fold in areal density by week 3. In contrast, the areal density of synaptic labeling by βAR404 barely doubled, in spite of the 30-fold increase in areal density of synapses. These results suggest that βAR undergo conformational changes during early postnatal periods, causing alterations in their relative antigenicity to the two antisera. Furthermore, the first 2 weeks appear to be characterized by modulation of earliest-formed synapses, and the subsequent phase is marked by addition of astrocytic responses that would be more diffuse temporally and spatially. Activation of βAR is recognized to increase visually evoked activity relative to spontaneous activity. Moreover, astrocytic βAR are documented to regulate extracellular concentrations of glutamate, ATP, and neurotrophic factors important for the formation of binocular connections. Thus, neuronal and astrocytic responses may, together and in tandem, facilitate strengthening of intracortical synaptic circuitry during early life.

In the CNS, fine processes of astrocytes often wrap around dendrites, axons and synapses, which provides an interface where neurons and astrocytes might interact. We have reported previously that selective Ca2+ elevation in astrocytes, by photolysis of caged Ca2+ by o-nitrophenyl-EGTA (NP-EGTA), causes a kainite receptor-dependent increase in the frequency of spontaneous inhibitory post-synaptic potentials (sIPSCs) in neighboring interneurons in hippocampal slices. However, tetrodotoxin (TTX), which blocks action potentials, reduces the frequency of miniature IPSCs (mIPSCs) in interneurons during Ca2+ uncaging by an unknown presynaptic mechanism. In this study we investigate the mechanism underlying the presynaptic inhibition. We show that Ca2+ uncaging in astrocytes is accompanied by a decrease in the amplitude of evoked IPSCs (eIPSCs) in neighboring interneurons. The decreases in eIPSC amplitude and mIPSC frequency are prevented by CPPG, a group II/III metabotropic glutamate receptor (mGluR) antagonist, but not by the AMPA/kainate and NMDA receptor antagonists CNQX/CPP. Application of either the group II mGluR agonist DCG IV or the group III mGluR agonist L-AP4 decreased the amplitude of eIPSCs by a presynaptic mechanism, and both effects are blocked by CPPG. Thus, activation of mGluRs mediates the effects of Ca2+ uncaging on mIPSCs and eIPSCs. Our results indicate that Ca2+-dependent release of glutamate from astrocytes can activate distinct classes of glutamate receptors and differentially modulate inhibitory synaptic transmission in hippocampal interneurons.

Synapse formation in the CNS is a complex process that involves the dynamic interplay of numerous signals exchanged between pre- and postsynaptic neurons as well as perisynaptic glia. Members of the neurotrophin family, which are widely expressed in the developing and mature CNS and are well-known for their roles in promoting neuronal survival and differentiation, have emerged as key synaptic modulators. However, the mechanisms by which neurotrophins modulate synapse formation and function are poorly understood. Here, we summarize our work on the role of neurotrophins in synaptogenesis in the CNS, in particular the role of these signaling molecules and their receptors, the Trks, in the development of excitatory and inhibitory hippocampal synapses. We discuss our results that demonstrate that postsynaptic TrkB signaling plays an important role in modulating the formation and maintenance of NMDA and GABAA receptor clusters at central synapses, and suggest that neurotrophin signaling coordinately modulates these receptors as part of mechanism that promotes the balance between excitation and inhibition in developing circuits. We also discuss our results that demonstrate that astrocytes promote the formation of GABAergic synapses in vitro by differentially regulating the development of inhibitory presynaptic terminals and postsynaptic GABAA receptor clusters, and suggest that glial modulation of inhibitory synaptogenesis is mediated by neurotrophin-dependent and -independent signaling. Together, these findings extend our understanding of how neuron–glia communication modulates synapse formation, maintenance and function, and set the stage for defining the cellular and molecular mechanisms by which neurotrophins and other cell–cell signals direct synaptogenesis in the developing brain.

Onset and offset of calcium current in response to short, depolarizing voltage pulses were studied in giant synaptic terminals of goldfish bipolar neurons. Tail-current decays were extremely rapid (80 μs at −70 mV), and exponentially slowed at more positive repolarization potentials. The amplitude of tail current following voltage pulses varied with the pulse amplitude, according to a Bolzmann distribution with a V1/2 of −27.6 mV and a slope factor of 13.8 mV. When interpreted with a Hodgkin-Huxley model, calcium-current onset was best described by m2 kinetics and a time constant (τm) of 0.62 ms at −10 mV. The kinetics of calcium-current onset and offset are at least two- to threefold faster than those described in other native cells. Combined with other recent data, the results suggest that the rapid kinetics may participate in a fast signaling mode in the goldfish ON-center pathway.

The molecular mechanism of volatile anaesthetic action on presynaptic glutamate release is not clear. An inhibitory effect on voltage-gated calcium channels has been proposed. The present study examines the effect of isoflurane on cytosolic free calcium and synaptic glutamate release from isolated nerve terminals. Synaptosomes from rat cerebral cortex were used. Glutamate was measured with a continuous fluorometric measurement in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. Isoflurane reduced the calcium-dependent glutamate release evoked by membrane depolarization with 4-aminopyridine in an inversely dose-dependent manner. The glutamate release was reduced by 56, 43 and 36% in response to isoflurane 0.5, 1.5 and 3.0%, respectively (for all: P<0.05). Membrane depolarization evoked a rise in cytosolic free calcium of ≈34%. Addition of isoflurane (0.5, 1.5 and 3.0%) produced no significant change in cytosolic free calcium. These results indicate that the isoflurane-induced reduction in presynaptic glutamate release is caused by other mechanisms than blocking voltage-gated calcium channels. As the release is inversely dose-dependent, two or more mechanisms could be involved.