In layer 4 of cat visual cortex, the monocular, concentric receptive fields of thalamic neurons, which relay retinal input to the cortex, are transformed into 'simple' cortical receptive fields that are binocular and selective for the precise orientation, direction of motion, and size of the visual stimulus. These properties are thought to arise from the pattern of connections from thalamic neurons, although anatomical studies show that most excitatory inputs to layer 4 simple cells are from recurrently connected circuits of cortical neurons. We examined single fibre inputs to spiny stellate neurons. We examined single fibre inputs to spiny stellate neurons in slices of cat visual cortex, and conclude that thalamocortical synapses are powerful and the responses they evoke are unusually invariant for central synapses. However, the responses to intracortical inputs, although less invariant, are strong enough to provide most of the excitation to simple cells in vivo. Our results suggest that the recurrent excitatory circuits of cortex may amplify the initial feedforward thalamic signal, subserving dynamic modifications of the functional properties of cortical neurons.

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NMDA receptors (NMDAR) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events.

Key points• N -Methyl-D-aspartate receptor (NMDAR)-dependent potentiation of synaptic transmission is widely accepted as a cellular model of learning and memory.• It is most often studied in the CA1 area of rat hippocampal slices where it comprises a decremental and a sustained phase, which are commonly referred to as short-term potentiation (STP) and long-term potentiation (LTP), respectively.• In this study we show for the first time that STP and LTP are triggered by the activation of different classes of NMDARs and that STP itself comprises two pharmacologically and kinetically distinct components.• We suggest that the mechanistic separation of STP and LTP is likely to have important functional implications in that these two forms of synaptic plasticity can subserve unique physiological functions in a behaving animal.Abstract Potentiation at synapses between CA3 and the CA1 pyramidal neurons comprises both transient and sustained phases, commonly referred to as short-term potentiation (STP or transient LTP) and long-term potentiation (LTP), respectively. Here, we utilized four subtype-selective N -methyl-D-aspartate receptor (NMDAR) antagonists to investigate whether the induction of STP and LTP is dependent on the activation of different NMDAR subtypes. We find that the induction of LTP involves the activation of NMDARs containing both the GluN2A and the GluN2B subunits. Surprisingly, however, we find that STP can be separated into two components, the major form of which involves activation of NMDARs containing both GluN2B and GluN2D subunits. These data demonstrate that synaptic potentiation at CA1 synapses is more complex than is commonly thought, an observation that has major implications for understanding the role of NMDARs in cognition. A. Volianskis and N. Bannister contributed equally to this work.

The aim of this study was to provide quantitative descriptions of the dendritic branching patterns of pyramidal neurones in the CA1 region of the rat hippocampus. Thirteen adult cells were filled with biocytin and reconstructed by using the light microscope. The number of basal trees arising from the soma of each cell ranged from two to eight. There was wide variation in the number of terminal segments per tree. Six cells had single apical trunks, and seven had trunks that bifurcated in stratum radiatum. The number of apical oblique trees ranged from nine to 30, with each tree usually showing a lower degree of branching than basal trees. Basal and oblique trees had similar branching patterns, with the majority of branch points occurring close to the origin of the tree. Both basal and oblique terminal segments were generally much longer than intermediate segments and constituted up to 90% of the combined dendritic length of the tree. The branching pattern of the apical tuft was different, with many relatively long intermediate segments; terminal segments contributed only some 66% of the combined dendritic length of these trees. The mean total combined dendritic length for six adult cells reconstructed and measured completely was 11,900 +/- 1,000 microns (standard deviation). The relative proportions of the different parts of the dendritic system, although not the total dendritic length, were correlated with the location of the soma relative to the cell body layer. Cells with somata close to the stratum pyramidale/stratum radiatum border had more dendrites terminating in stratum radiatum and fewer in stratum oriens than cells with somata further from it.