Introduction to synaptic circuits, Gordon M.Shepherd and Christof Koch membrane properties and neurotransmitter actions, David A.McCormick peripheral ganglia, Paul R.Adams and Christof Koch spinal cord - ventral horn, Robert E.Burke olfactory bulb, Gordon M.Shepherd, and Charles A.Greer retina, Peter Sterling cerebellum, Rodolfo R.Llinas and Kerry D.Walton thalamus, S.Murray Sherman and Christof Koch basal ganglia, Charles J.Wilson olfactory cortex, Lewis B.Haberly hippocampus, Thomas H.Brown and Anthony M.Zador neocortex, Rodney J.Douglas and Kevan A.C.Martin Gordon M.Shepherd. Appendix: Dendretic electrotonus and synaptic integration.

The synaptic organization of the brain

Of the many possible functions of the macaque monkey primary visual cortex (striate cortex, area 17) two are now fairly well understood. First, the incoming information from the lateral geniculate bodies is rearranged so that most cells in the striate cortex respond to specifically oriented line segments, and, second, information originating from the two eyes converges upon single cells. The rearrangement and convergence do not take place immediately, however: in layer IVc, where the bulk of the afferents terminate, virtually all cells have fields with circular symmetry and are strictly monocular, driven from the left eye or from the right, but not both; at subsequent stages, in layers above and below IVc, most cells show orientation specificity, and about half are binocular. In a binocular cell the receptive fields in the two eyes are on corresponding regions in the two retinas and are identical in structure, but one eye is usually more effective than the other in influencing the cell; all shades of ocular dominance are seen. These two functions are strongly reflected in the architecture of the cortex, in that cells with common physiological properties are grouped together in vertically organized systems of columns. In an ocular dominance column all cells respond preferentially to the same eye. By four independent anatomical methods it has been shown that these columns have the from of vertically disposed alternating left-eye and right-eye slabs, which in horizontal section form alternating stripes about 400 $\mu $m thick, with occasional bifurcations and blind endings. Cells of like orientation specificity are known from physiological recordings to be similarly grouped in much narrower vertical sheeet-like aggregations, stacked in orderly sequences so that on traversing the cortex tangentially one normally encounters a succession of small shifts in orientation, clockwise or counterclockwise; a 1 mm traverse is usually accompanied by one or several full rotations through 180 degrees, broken at times by reversals in direction of rotation and occasionally by large abrupt shifts. A full complement of columns, of either type, left-plus-right eye or a complete 180 degrees sequence, is termed a hypercolumn. Columns (and hence hypercolumns) have roughly the same width throughout the binocular part of the cortex. The two independent systems of hypercolumns are engrafted upon the well known topographic representation of the visual field. The receptive fields mapped in a vertical penetration through cortex show a scatter in position roughly equal to the average size of the fields themselves, and the area thus covered, the aggregate receptive field, increases with distance from the fovea. A parallel increase is seen in reciprocal magnification (the number of degrees of visual field corresponding to 1 mm of cortex). Over most or all of the striate cortex a movement of 1-2 mm, traversing several hypercolumns, is accompanied by a movement through the visual field about equal in size to the local aggregate receptive field. Thus any 1-2 mm block of cortex contains roughly the machinery needed to subserve an aggregate receptive field. In the cortex the fall-off in detail with which the visual field is analysed, as one moves out from the foveal area, is accompanied not by a reduction in thickness of layers, as is found in the retina, but by a reduction in the area of cortex (and hence the number of columnar units) devoted to a given amount of visual field: unlike the retina, the striate cortex is virtually uniform morphologically but varies in magnification. In most respects the above description fits the newborn monkey just as well as the adult, suggesting that area 17 is largely genetically programmed. The ocular dominance columns, however, are not fully developed at birth, since the geniculate terminals belonging to one eye occupy layer IVc throughout its length, segregating out into separate columns only after about the first 6 weeks, whether or not the animal has visual experience. If one eye is sutured closed during this early period the columns belonging to that eye become shrunken and their companions correspondingly expanded. This would seem to be at least in part the result of interference with normal maturation, though sprouting and retraction of axon terminals are not excluded.

Ferrier Lecture: Functional Architecture of Macaque Monkey Visual Cortex

Directionally selective single units have recently been found in the cerebral cortex of cats (Hubel, 1959; Hubel & Wiesel, 1959, 1962), the optic tectum of frogs and pigeons (Lettvin, Maturana, McCulloch & Pitts, 1959; Maturana & Frenk, 1963), and the retinae of rabbits (Barlow & Hill, 1963; Barlow, Hill & Levick, 1964). The term 'directionally selective' means that a unit gives a vigorous discharge of impulses when a stimulus object is moved through its receptive field in one direction (called the preferred direction), whereas motion in the reverse direction (called null) evokes little or no response. The preferred direction differs in different units, and the activity of a set of such units signals the direction of movement of objects in the visual field. In the rabbit the preferred and null directions cannot be predicted from a map of the receptive field showing the regions yielding on or off-responses to stationary spots. Furthermore, the preferred direction is unchanged by changing the stimulus; in particular, reversing the contrast of a spot or a black-white border does not reverse the preferred direction. Hubel & Wiesel (1962) thought that the directional selectivity of the cat's cortical neurons could be explained by the asymmetrical arrangement of on and off zones in the receptive field, and the simple interaction of effects summated over these zones, but the foregoing results rule out this explanation, at least in the rabbit's retina (Barlow & Hill, 1963). In the present paper we go on from this point to describe experiments which show, first, that directional selectivity is not due to optical aberrations of some kind and, secondly, that it is not a simple matter of the latency of response varying systematically across the receptive field. After these negative results we describe experiments upon the organization of directional selectivity within the receptive field, and upon its mechanism. These lead us to the conclusion that the ganglion cells responding to a

The mechanism of directionally selective units in rabbit's retina.

The problem discussed is the relationship between the firing of single neurons in sensory pathways and subjectively experienced sensations. The conclusions are formulated as the following five dogmas:To understand nervous function one needs to look at interactions at a cellular level, rather than either a more macroscopic or microscopic level, because behaviour depends upon the organized pattern of these intercellular interactions.The sensory system is organized to achieve as complete a representation of the sensory stimulus as possible with the minimum number of active neurons.Trigger features of sensory neurons are matched to redundant patterns of stimulation by experience as well as by developmental processes.Perception corresponds to the activity of a small selection from the very numerous high-level neurons, each of which corresponds to a pattern of external events of the order of complexity of the events symbolized by a word.High impulse frequency in such neurons corresponds to high certainty that t...

Single units and sensation: a neuron doctrine for perceptual psychology?

Three-dimensional (3D) structural information on many length scales is of central importance in biological research. Excellent methods exist to obtain structures of molecules at atomic, organelles at electron microscopic, and tissue at light-microscopic resolution. A gap exists, however, when 3D tissue structure needs to be reconstructed over hundreds of micrometers with a resolution sufficient to follow the thinnest cellular processes and to identify small organelles such as synaptic vesicles. Such 3D data are, however, essential to understand cellular networks that, particularly in the nervous system, need to be completely reconstructed throughout a substantial spatial volume. Here we demonstrate that datasets meeting these requirements can be obtained by automated block-face imaging combined with serial sectioning inside the chamber of a scanning electron microscope. Backscattering contrast is used to visualize the heavy-metal staining of tissue prepared using techniques that are routine for transmission electron microscopy. Low-vacuum (20–60 Pa H2O) conditions prevent charging of the uncoated block face. The resolution is sufficient to trace even the thinnest axons and to identify synapses. Stacks of several hundred sections, 50–70 nm thick, have been obtained at a lateral position jitter of typically under 10 nm. This opens the possibility of automatically obtaining the electron-microscope-level 3D datasets needed to completely reconstruct the connectivity of neuronal circuits.

/pdf/serial-block-face-scanning-electron-microscopy-to-380lz5nusy.pdf

Serial block−face scanning electron microscopy to reconstruct three−dimensional tissue nanostructure

Retinal ganglion cells responding selectively to direction and speed of image motion in the rabbit.

1. The mean rate, impulse interval distribution, and pulse number distribution of the maintained discharge of ganglion cells in the retina of the cat have been studied after prolonged adaptation at different luminance levels.2. From a state of complete dark adaptation up to a luminance of about 5 x 10(-3) cd/m(2) (viewed through a 7 mm(2) pupil) the mean rate of on-centre units increases. From darkness up to a somewhat higher luminance the mean rate of some off-centre units decreases, but others show little change.3. Above 10(-2) cd/m(2) the mean rate ceases to show a regular relation with adaptation level. On units often decrease and then increase again at a higher level. Rhythmical fluctuations are common near 10(-2) cd/m(2), especially if the retina is not in first class condition. Mean rates above 70/sec and below 1/sec are very rare at any adaptation level.4. Over the range where mean rate increases monotonically with adaptation level, it is shown that the surround of on-centre units does not inhibit and off responses cannot be elicited. When the monotonic increase is slowed or reversed it becomes possible to elicit responses from the surround. We suspect that the surround exerts a sustained, tonic, inhibiting effect at higher adaptation levels, thus holding down the maintained discharge.5. There are rare units, forming less than 1% of those isolated, that show a regularly increasing frequency with increase of adaptation level above 10(-2) cd/m(2). These units have concentric ;on' and ;off' zones in their receptive fields, but the responses to rapidly changing stimuli are sluggish and they have an unusually regular maintained discharge. They have been tentatively called ;luminance units'.6. The impulse-interval and pulse-number distributions of on-centre units change predictably with adaptation level; the variance of the pulse number distribution is usually several times the mean at very low adaptation levels, but only a fraction of the mean at high levels. Off-centre units do not show predictable changes. Luminance units fire more regularly, and have narrower pulse-number and impulse interval distributions than other concentric units.7. A simple model is proposed to account for the statistical characteristics of the maintained discharge of on-centre units.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1969.sp008836

Changes in the maintained discharge with adaptation level in the cat retina

1. Responses of cat retinal ganglion cells have been examined with a view to specifying the characteristics that limit the detection of light stimuli.

2. Threshold is defined as the weakest stimulus that can be reliably detected by examination of the output from a retinal ganglion cell; it depends upon (a) the quantum/spike ratio, which is the mean number of additional quantal absorptions required to produce an additional impulse, (b) the temporal course of the response, which determines the time interval within which the maintained discharge is modified, and (c) the statistical distribution of the number of impulses that occur in this time interval in the absence of the stimulus.

3. The quantum/spike ratio changes greatly when adapting luminance is changed, and this is the predominant factor accounting for changes in increment threshold.

4. The time course of the response changes with adaptation level and area of the stimulus. This may account for the changes in temporal integration that occur in analogous psychophysical experiments.

5. Changes in the irregularity of the maintained discharge also affect the threshold of single ganglion cells. This is only a minor factor in the conditions of most of our experiments, but it may be important when unstabilized images and non-equilibrium adaptation conditions are encountered.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1969.sp008679

Three factors limiting the reliable detection of light by retinal ganglion cells of the cat

1. The slope of curves relating the log increment threshold to log background luminance in cat retinal ganglion cells is affected by the area and duration of the test stimulus, as it is in human pyschophysical experiments. 2. Using large area, long duration stimuli the slopes average 0-82 and approach close to 1 (Weber's Law) in the steepest cases. Small stimuli gave an average of 0-53 for on-centre units using brief stimuli, and 0-56 for off-centre units, using long stimuli. Slopes under 0-5 (square root law) were not found over an extended range of luminances. 3. On individual units the slope was generally greater for larger and longer test stimulus, but no unit showed the full extent of change from slope of 0-5 to slope of 1. 4. The above differences hold for objective measures of quantum/spike ratio, as well as for thresholds either judged by ear or assessed by calculation. 5. The steeper slope of the curves for large area, long duration test stimuli compared with small, long duration stimuli, is associated with the increased effectiveness of antagonism from the surround at high backgrounds. This change may be less pronounced in off-centre units, one of which (probably transient Y-type) showed no difference of slope, and gave parallel area-threshold curves at widely separated background luminances, confirming the importance of differential surround effectiveness in changing the slope of the curves. 6. In on-centre units, the increased relative effectiveness of the surround is associated with the part of the raised background light that falls on the receptive field centre. 7. It is suggested that the variable surround functions as a zero-offset control that sets the threshold excitation required for generating impulses, and that this is separate from gain-setting adaptive mechanisms. This may be how ganglion cells maintain high incremental sensitivity in spite of a strong maintained excitatory drive that would otherwise cause compressive response non-linearities.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1976.sp011492

W. R. Levick

Papers

The mechanism of directionally selective units in rabbit's retina.

Retinal ganglion cells responding selectively to direction and speed of image motion in the rabbit.

Changes in the maintained discharge with adaptation level in the cat retina

Three factors limiting the reliable detection of light by retinal ganglion cells of the cat

Threshold setting by the surround of cat retinal ganglion cells.