Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.

The mushroom bodies of the bee are paired neuropils in the dorsal part of the brain. Each is composed of the arborizations of over 17 x 10 4 small interneurons of similar architecture called Kenyon cells. Golgi staining demonstrates that these neurons can be divided into five groups distinguished on the basis of their dendritic specializations and geometry. The mushroom body neuropils each consist of a pair of cup-shaped structures, the calyces, connected by two short fused stalks, the pedunculus, to two lobes, the α- and β-lobes. Each calyx is formed from three concentric neuropil zones, the basal ring, the collar and the lip. The calyces are organized in a polar fashion; within the calyces each of the five categories of Kenyon cell has a distribution limited to particular polar contours. The dendritic volumes of neighbouring Kenyon cells arborizing within each individual contour are greatly overlapped. Fibres from groups of neighbouring cells within a calycal contour are gathered into bundles that project into the pedunculus, each fibre dividing to enter both the the α- and β-lobes. The pedunculus and the lobes are conspicuously layered. Kenyon cells with neighbouring dendritic fields within the same calycal contour occupy a single layer in the pedunculus and lobes. Thus the two- polar organization of the calyces is transformed into a Cartesian map within the pedunculus, which continues into the α- and β-lobes. The calyx receives input fibres from both the antennal lobes and the optic neuropils. The branching patterns of these cells reflect the polar organization of the calyces as their terminals are restricted to one or more of the three gross compartments of the calycal neuropil. The course of these tracts and the morphologies of the fibres that they contain are described. Cells considered to represent outputs from the mushroom bodies arborize in the pedunculus and α- and β-lobes. Generally the arborizations of the output neurons reflect the layered organization of these neuropils. Fibres from the two lobes run to the anterior median and lateral protocerebral neuropil, and the anterior optic tubercle. Additionally there is an extensive network of feedback interneurons that inter- connect the α- and β-lobes with the ipsi- and contralateral calyces. Many individual neurons have branches in both the α- and β-lobes and in the pedunculus. The pathways and geometries of the fibres subserving the two lobes are described. The hypothesis of Vowles (1955) that the individual lobes represent a separation of sensory and motor output areas is shown to be incorrect. The anatomy of the bee’s mushroom bodies suggests that they process second-order antennal and fourth- and higher-order visual information. The feedback pathways are discussed as possible means of creating long-lasting after-effects which may be important in complex timing processes and possibly the formation of short-term memory.

The retinal pigment epithelium (RPE) plays an essential role in the normal development of the underlying neural retina, but the mechanisms by which this regulation occurs are largely unknown. Ca2+ transients, induced by the neurotransmitter ATP acting on purinergic receptors, both increase proliferation and stimulate DNA synthesis in neural retinal progenitor cells. Here, we show that the RPE regulates proliferation in the underlying neural retina by the release of a soluble factor and identify that factor as ATP. Further, we show that this ATP is released by efflux through gap junction connexin 43 hemichannels, the opening of which is evoked by spontaneous elevations of Ca2+ in trigger cells in the RPE. This release mechanism is localized within the RPE cells to the membranes facing the neural retina, a location ideally positioned to influence neural retinal development. ATP released from RPE hemichannels speeds both cell division and proliferation in the neural retina.

No abstract

A major function of glial cells in the central nervous system is to buffer the extracellular potassium concentration, [K+]o. A local rise in [K+]o causes potassium ions to enter glial cells, which have membranes that are highly permeable to K+; potassium then leaves the glial cells at other locations where [K+]o has not risen. We report here the first study of the individual ion channels mediating potassium buffering by glial cells. The patch-clamp technique was employed to record single channel currents in Müller cells, the radial glia of the vertebrate retina. Those cells have 94% of their potassium conductance in an endfoot apposed to the vitreous humour, causing K+ released from active retinal neurones to be buffered preferentially to the vitreous. Recordings from patches of endfoot and cell body membrane show that a single type of inward-rectifying K+ channel mediates potassium buffering at both cell locations. The non-uniform density of K+ conductance is due to a non-uniform distribution of one type of K+ channel, rather than to the cell expressing high conductance channels at the endfoot and low conductance channels elsewhere on the cell.

The development of the central nervous system is dependent on spontaneous action potentials and changes in [Ca2+]i occurring in neurons [1-4]. In the mammalian retina, waves of spontaneous electrical activity spread between retinal neurons, raising [Ca2+]i as they pass [5-7]. In the ferret retina, the first spontaneous Ca2+ waves have been reported at postnatal day 2 and are thought to result from the Ca2+ influx associated with bursts of action potentials seen in ganglion cells at this time [5-7]. These waves depend on depolarisation produced by voltage-gated sodium channels, but their initiation and/or propagation also depends upon nicotinic cholinergic synaptic transmission between amacrine cells and ganglion cells [8]. Here, we report contrasting results for the chick retina where Ca2+ transients are seen at times before retinal synapse formation but when there are extensive networks of gap junctions. These Ca2+ transients do not require nicotinic cholinergic transmission but are modulated by acetylcholine (ACh), dopamine and glycine. Furthermore, they propagate into the depth of the retina, suggesting that they are not restricted to ganglion and amacrine cells. The transients are abolished by the gap-junctional blocker octanol. Thus, the Ca2+ transients seen early in chick retinal development are triggered and propagate in the absence of synapses by a mechanism that involves several neurotransmitters and gap junctions.

Tonic activation of excitatory and inhibitory receptors, by the ambient concentration of neurotransmitters in the extracellular space of the brain, has been suggested to underlie phenomena as diverse as relapse to cocaine use by reward pathways in the striatum, sparse coding of motor information in the cerebellum, and control of the development of the cerebral and cerebellar cortices. Here we assess the mechanisms which may determine the ambient levels of excitatory and inhibitory neurotransmitters, and consider their likely effect on information processing.

SUMMARY1. Whole-cell patch clamping was used to study the membrane properties of isolated bipolar cells and the currents evoked in them by putative retinal neurotransmitters.2. Isolated bipolar cells show an approximately ohmic response to voltage steps over most of the physiological response range, with an average input resistance of 1-3 GfS and resting potential of -35 mV. These values are underestimates because of the shunting effect of the seal between the patch electrode and the cell membrane. Depolarization beyond -30 mV produces rapid activation (10-100 ms) ofan outward current (carried largely by potassium ions), which then inactivates slowly (05-2 s).3. Of five candidates for the photoreceptor transmitter, four (aspartate, Nacetylhistidine, cadaverine, putrescine) had no effect on bipolar cells. The fifth substance, L-glutamate, opened ionic channels with a mean reversal potential of -12 mV in some cells (presumed hyperpolarizing bipolar cells), and closed channels with a mean reversal potential, of -13 mV in other cells (presumed depolarizing bipolar cells); 4. The conductance increase induced by glutamate in presumed hyperpolarizing bipolar cells was associated with an increase in membrane current noise. Noise analysis suggested a single-channel conductance for the glutamate-gated channel of 5.4 pS. The power spectrum of the noise increase required the sum of two Lorentzian curves to fit it, suggesting that the channel can exist in three states.5. The conductance decrease induced by glutamate in presumed depolarizing bipolar cells was associated with a decrease in membrane current noise that could be described as the sum of two Lorentzian spectra, and which suggested a singlechannel conductance of 11 pS. The noise decrease implies that the channels closed by glutamate are not all open in the absence of the transmitter.6. GABA (y-aminobutyric acid) and glycine, transmitters believed to mediate lateral inhibition in the retina, open chloride channels in isolated bipolar cells, and increase the membrane current noise. Noise analysis suggested that the channels gated by GABA and glycine have conductances of 4-4 and 7-5 pS respectively. The noise spectra required the sum of two Lorentzian curves to fit them.t To whom all reprint requests should be sent.