Department of Biological Sciences and Neurosciences Graduate Program, University of Southern California, Los Angeles, CA 90089-2520, USA
Address correspondence to Judith A. Hirsch, HNB 328, M-C 2520, Department of Biological Sciences, University of Southern California, 3641 Watt Way, Los Angeles, CA 90089, USA. Email: jhirsch{at}usc.edu.
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Abstract |
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Introduction |
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Synaptic Structure of Receptive Fields of Thalamic Relay Cells and Cortical Simple Cells |
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Structure of the Thalamic Receptive Field |
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Our whole-cell recordings have permitted direct visualization of the patterns of excitatory and inhibitory synaptic input that define the push and the pull (McIlwain and Creutzfeldt, 1967). Figure 1
depicts records from an off center relay cell in layer A of the lateral geniculate nucleus; the stimulus was a series of bright and dark squares briefly flashed, one at a time, in pseudorandom order 16 times on 16 x 16 grid (Jones and Palmer, 1987
; Hirsch, 1995
). Figure 1B
shows intracellular responses to dark and 1C to bright stimuli that fell in the peak of the receptive field center (top), here mapped as a contour plot with stimulus sign and position indicated within. Beneath each map are two individual trials of the stimulus, with the average of all trials shown in bold. Every dark spot that fell in the center evoked a depolarization capped by action potentials. This initial excitation, or push, was followed by a hyperpolarization, or pull, that, after a delay imposed by the circuitry (Cai et al., 1997
), corresponded to the withdrawal of the stimulus. The introduction and removal of bright stimuli flashed in the same place produced the opposite response, an initial hyperpolarization followed by a depolarizing rebound.
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Structure of the Simple Receptive Field: Excitatory and Inhibitory Cells |
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Figure 2 illustrates properties of a spiny stellate cell in cortical layer 4 (Fig. 2C
); the design of the figure is as for Figure 1
. Individual cortical responses to bright and dark stimuli flashed at the peak of the on subregion strongly resemble thalamic responses to the same stimuli (Fig. 2A,B
). The layout of the entire simple field is shown in Figure 2D
as an array of trace pairs with the subregions indicated by dotted lines. At a glance, it is clear that the motif of pushpull dominates the receptive field (as for the relay cell, stimuli that spanned adjacent subregions evoked composite responses).
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The PushPull Rationale |
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The model is also attractive for its conservation of a single mechanism, pushpull, from retina to thalamus to cortex and for the simplicity of its basic circuit (Hubel and Wiesel, 1962; Palmer and Davis, 1981
; Jones and Palmer, 1987
; Ferster, 1988
; Hirsch et al., 1998
; Troyer et al., 1998
; Ferster and Miller, 2000
). Figure 4
presents a wiring diagram for pushpull. A simple subregion is made from aligned rows of thalamic centers by means of relay cells that converge on a single cortical target to generate the push. The pull is made by thalamic input routed through cortical interneurons whose simple receptive fields have shapes similar to those of their postsynaptic partners but whose subregions have the reverse preference for stimulus contrast.
Although this circuit (Fig. 4) has yet to be demonstrated explicitly, it continues to receive experimental support. Certainly, our finding of the point-by-point iteration of push and pull throughout the simple field supports the model, as do earlier physiological studies (Palmer and Davis, 1981
; Ferster, 1986
, 1988
; Heggelund, 1986
; Jones and Palmer, 1987
; Tolhurst and Dean, 1987
; De Angelis et al., 1995
) and the placement of the simple field in thalamorecipient zones (Hubel and Wiesel, 1962
; Gilbert, 1977
; Bullier and Henry, 1979
; Ferster and Lindstrom, 1983
; Martinez et al., 1998
). More support comes from crosscorrelation studies that have shown that thalamic relay cells and cortical simple cells, whose respective receptive field centers and subregions have the same sign and spatial position, are likely to be monosynaptically connected (Tanaka, 1983
; Reid and Alonso, 1995
; Alonso et al., 2001
). As well, time-courses of thalamic and cortical responses are similar (Cai et al., 1997
; Hirsch et al., 1998
, 2002
; Alonso et al., 2001
). Further, recordings from thalamic afferents in silenced cortex suggest that these are organized in appropriately oriented rows (Chapman et al., 1991
) and intracellular recordings from silenced cortex suggest that the thalamus provides a substantial fraction of the tuned cortical response (Ferster et al., 1996
; Chung and Ferster, 1998
). Lastly, a missing piece of evidence for the model had been the demonstration of cells that could provide the pull, which is thought to result from intracortical inhibition (Ferster, 1986
; Borg-Graham et al., 1998
; Hirsch et al., 1998
; Anderson et al., 2001
). We, however, have now shown that such inhibitory simple cells exist see Figures 3 and 4
(Hirsch et al., 2000
).
Another line of support for the role of pushpull comes from comparisons of the shape of the receptive field with the degree of orientation tuning. The model predicts that as simple subregions become more elongated, thereby increasing the ratio between the amounts of excitation recruited by the preferred versus orthogonal stimulus, orientation selectivity sharpens. This expectation, to a first approximation, has been corroborated both by extracellular recordings (Jones and Palmer, 1987; Gardner et al., 1999
) and intracellular recordings (Martinez et al., 1998
, 2002
; Lampl et al., 2001
). All told, the pushpull circuit appears to lay the foundation for orientation tuning that auxiliary mechanisms help refine.
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Laminar Differences in Synaptic Physiology |
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Our approach was to compare response of cells in layer 4 to layer 2 + 3, which receives dense input from layer 4 but virtually none from the lateral geniculate. Although, most cells in layer 4 are simple, a small number of them are complex. Complex receptive fields lack segregated on and off subregions; they may respond to bright and dark stimuli positioned the same place in the field pushpush or stimuli of only one contrast pushnull (Hubel and Wiesel, 1962; Movshon et al., 1978b
; Palmer and Davis, 1981
; De Angelis et al., 1995
). We found that all cells in layer 4, simple and complex alike, seemed to capture and relay thalamic input that is, responses reliably reprised the time-course of each thalamic volley evoked by the flashed stimulus and typically crossed the threshold for firing, for example Figure 2
(Hirsch et al., 1998
; Hirsch et al., 2002
).
At later stages of processing, such as layer 2 + 3, complex cells compose the dominant, if not the entire, population (Hubel and Wiesel, 1962; Gilbert, 1977
; Movshon et al., 1978b
; Ferster and Lindstrom, 1983
). We found that the synaptic physiology of response in layer 2 + 3 was very different from that in layer 4, despite dense projections from that layer (Gilbert and Wiesel, 1979
; Martin and Whitteridge, 1984
; Hirsch et al., 2002
); that is, the synaptic physiology of response seemed to depend on position in the cortical microcircuit rather than the spatial structure of the receptive field. In the superficial layers, postsynaptic responses to the sparse stimulus were brief, labile and did not reprise antecedent activity. Figure 5
illustrates the case of a pyramidal cell near the top of layer 2 + 3. Responses to the dark spots lasted less than half the duration typical of layer 4 (Fig. 5B
, first and third trace); for a fuller and quantitative description of such behavior see previously published work (Hirsch et al., 2002
). As well, the stimulus often failed to evoke a response (e.g. Fig. 5B
, second trace). This impoverishment of response is best illustrated for the case of bright stimuli (Fig. 5C
); these had no effect at all (traces illustrate ongoing changes in the membrane potential). Furthermore, almost half of the superficial cells (n = 11) we have tested failed to respond to the sparse stimulus at all, though all cells had healthy membranes and responded vigorously to rich stimuli such as moving bars (Hirsch et al., 2002
).
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In fact, work in vitro and in vivo has revealed diverse mechanisms operating at the level of the dendrite or the synapse proper that regulate communication from one cell to the next. These processes include changes in dendritic membrane properties induced by local inputs (Fatt and Katz, 1951; Bernander et al., 1991
; Pare et al., 1998
; Destexhe and Pare, 1999
) and differential strength and security of transmission at various connections (Allen and Stevens, 1994
; Stratford et al., 1996
; Feldmeyer et al., 1999
, 2002
; Gil et al., 1999
; Feldmeyer and Sakmann, 2000
). It is likely that many such mechanisms play a part in gating the intracortical transfer of information (Hirsch et al., 2002
).
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Conclusion |
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The extent to which the synaptic physiology of laminar processing in the visual cortex resembles that in other sensory systems is not yet clear, largely because studies of synaptic integration in vivo are few. The combined results of varied studies of the barrel cortex, however, suggest a measure of similarity between somatosensory and visual areas specifically that processing within the thalamorecipent zone is more robust than at later stages (Moore and Nelson, 1998; Brumberg et al., 1999
; Feldmeyer et al., 1999
, 2002
; Gil et al., 1999
; Zhu and Connors, 1999
; Feldmeyer and Sakmann, 2000
; Swadlow and Gusev, 2000
).
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Footnotes |
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References |
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Allen C, Stevens CF (1994) An evaluation of causes of unreliability of synaptic transmission. Proc Natl Acad Sci USA 9:1038010383.
Alonso JM, Usrey WM, Reid RC (2001) Rules of connectivity between geniculate cells and simple cells in cat primary visual cortex. J Neurosci 21:40024015.
Anderson JS, Lampl I, Gillespie DC, Ferster D (2001) Membrane potential and conductance changes underlying length tuning of cells in cat primary visual cortex. J Neurosci 21:21042112.
Ben-Yishai R, Bar-Or RL, Sompolinsky H (1995) Theory of orientation tuning in visual cortex. Proc Natl Acad Sci USA 92:38443848.
Bernander O, Douglas RJ, Martin KA, Koch C (1991) Synaptic background activity influences spatiotemporal integration in single pyramidal cells. Proc Natl Acad Sci USA 88:1156911573.[Abstract]
Borg-Graham LJ, Monier C, Fregnac Y (1998) Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393:369373.[CrossRef][ISI][Medline]
Brumberg JC, Pinto DJ, Simons DJ (1999) Cortical columnar processing in the rat whisker-to-barrel system. J Neurophysiol 82:18081817.
Bullier J, Henry GH (1979) Laminar distribution of first-order neurons and afferent terminals in cat striate cortex. J Neurophysiol 42:12711281.
Bullier J, Norton TT (1979) Comparison of receptive-field properties of X and Y ganglion cells with X and Y lateral geniculate cells in the cat. J Neurophysiol 42:274291.
Cai D, DeAngelis GC, Freeman RD (1997) Spatiotemporal receptive field organization in the lateral geniculate nucleus of cats and kittens. J Neurophysiol 78:10451061.
Callaway EM (1998) Local circuits in primary visual cortex of the macaque monkey. Annu Rev Neurosci 21:4774.[CrossRef][ISI][Medline]
Chapman B, Zahs KR, Stryker MP (1991) Relation of cortical cell orientation selectivity to alignment of receptive fields of the geniculo-cortical afferents that arborize within a single orientation column in ferret visual cortex. J Neurosci 11:13471358.[Abstract]
Chung S, Ferster D (1998) Strength and orientation tuning of the thalamic input to simple cells revealed by electrically evoked cortical suppression. Neuron 20:11771189.[ISI][Medline]
De Angelis GC, Ohzawa I, Freeman RD (1993a) Spatiotemporal organization of simple-cell receptive fields in the cats striate cortex. I. General characteristics and postnatal development. J Neurophysiol 69:1091117.
De Angelis GC, Ohzawa I, Freeman RD (1993b) Spatiotemporal organization of simple-cell receptive fields in the cats striate cortex. II. Linearity of temporal and spatial summation. J Neurophysiol 69:11181135.
De Angelis GC, Ohzawa I, Freeman RD (1995) Receptive field dynamics in central visual pathways. Trends Neurosci 18:451458.[CrossRef][ISI][Medline]
Debanne D, Shulz DE, Fregnac Y (1998) Activity-dependent regulation of on and off responses in cat visual cortical receptive fields. J Physiol 508:523548.
Destexhe A, Pare D (1999) Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. J Neurophysiol 81:15311547.
Douglas RJ, Koch C, Mahowald M, Martin KA, Suarez HH (1995) Recurrent excitation in neocortical circuits. Science 269:981985.[ISI][Medline]
Fatt P, Katz B (1951) An analysis of the endplate potential recorded with an intracellular electrode. J Physiol 115:320370.[ISI]
Feldmeyer D, Sakmann B (2000) Synaptic efficacy and reliability of excitatory connections between the principal neurones of the input (layer 4) and output layer (layer 5) of the neocortex. J Physiol 525:3139.
Feldmeyer D, Egger V, Lubke J, Sakmann B (1999) Reliable synaptic connections between pairs of excitatory layer 4 neurones within a single barrel of developing rat somatosensory cortex. J Physiol 521:169190.
Feldmeyer D, Lubke J, Silver RA, Sakmann B (2002) Synaptic connections between layer 4 spiny neuronelayer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column. J Physiol 538:803822.
Ferster D (1986) Orientation selectivity of synaptic potentials in neurons of cat primary visual cortex. J Neurosci 6:12841301.[Abstract]
Ferster D (1988) Spatially opponent excitation and inhibition in simple cells of the cat visual cortex. J Neurosci 8:11721180.[Abstract]
Ferster D, Lindstrom S (1983) An intracellular analysis of geniculo-cortical connectivity in area 17 of the cat. J Physiol 342:181215.[Abstract]
Ferster D, Miller KD (2000) Neural mechanisms of orientation selectivity in the visual cortex. Annu Rev Neurosci 23:441471.[CrossRef][ISI][Medline]
Ferster D, Chung S, Wheat H (1996) Orientation selectivity of thalamic input to simple cells of cat visual cortex. Nature 380:249252.[CrossRef][ISI][Medline]
Fitzpatrick D (1996) The functional organization of local circuits in visual cortex: insights from the study of tree shrew striate cortex. Cereb Cortex 6:329341.[Abstract]
Frégnac Y (1996) Dynamics of functional connectivity in visual cortical networks: an overview. J Physiol 90:113139.
Gardner JL, Anzai A, Ohzawa I, Freeman RD (1999) Linear and nonlinear contributions to orientation tuning of simple cells in the cats striate cortex. Vis Neurosci 16:11151121.[CrossRef][ISI][Medline]
Gil Z, Connors BW, Amitai Y (1999) Efficacy of thalamocortical and intracortical synaptic connections: quanta, innervation, and reliability. Neuron 23:385397.[ISI][Medline]
Gilbert CD (1977) Laminar differences in receptive field properties of cells in cat primary visual cortex. J Physiol 268:391421.[ISI][Medline]
Gilbert CD, Wiesel TN (1979) Morphology and intracortical projections of functionally characterised neurones in the cat visual cortex. Nature 280:120125.[ISI][Medline]
Heggelund P (1986) Quantitative studies of enhancement and suppression zones in the receptive field of simple cells in cat striate cortex. J Physiol 373:293310.[Abstract]
Hirsch JA (1995) Synaptic integration in layer IV of the ferret striate cortex. J Physiol 483:183199.[Abstract]
Hirsch JA, Alonso JM, Reid RC, Martinez LM (1998) Synaptic integration in striate cortical simple cells. J Neurosci 18:95179528.
Hirsch JA, Martinez LM, Alonso JM, Desai K, Pillai C, Pierre C (2000) Simple and complex inhibitory cells in layer 4 of cat visual cortex. Soc Neurosci Abstr 26:108.
Hirsch JA, Martinez LM, Alonso JM, Desai K, Pillai C, Pierre C (2002) Synaptic physiology of the flow of information in the cats visual cortex in vivo. J Physiol 540:235250.
Hubel DH, Wiesel TN (1961) Integrative action in the cats lateral geniculate body. J Physiol. 155:385398.[ISI][Medline]
Hubel DH, Wiesel TN (1962) Receptive fields, binocular interaction and functional architecture in the cats visual cortex. J Physiol 160:106154.[ISI][Medline]
Humphrey AL, Sur M, Uhlrich DJ, Sherman SM (1985) Projection patterns of individual X- and Y-cell axons from the lateral geniculate nucleus to cortical area 17 in the cat. J Comp Neurol 233:159189.[ISI][Medline]
Jones JP, Palmer LA (1987) The two-dimensional spatial structure of simple receptive fields in cat striate cortex. J Neurophysiol 58:11871211.
Kuffler S (1953) Discharge patterns and functional organization of the mammalian retina. J Neurophysiol 16:3768.
Lampl I, Anderson JS, Gillespie DC, Ferster D (2001) Prediction of orientation selectivity from receptive field architecture in simple cells of cat visual cortex. Neuron 30:263274.[CrossRef][ISI][Medline]
LeVay S, Gilbert CD (1976) Laminar patterns of geniculocortical projection in the cat. Brain Res 113:119.[CrossRef][ISI][Medline]
McIlwain JT, Creutzfeldt OD (1967) Microelectrode study of synaptic excitation and inhibition in the lateral geniculate nucleus of the cat. J Neurophysiol 30:131.[ISI]
McLaughlin D, Shapley R, Shelley M, Wielaard DJ (2000) A neuronal network model of macaque primary visual cortex (V1): orientation selectivity and dynamics in the input layer 4Calpha.Proc Natl Acad Sci USA 97:80878092.
Martin KA, Whitteridge D (1984) Form, function and intracortical projections of spiny neurones in the striate visual cortex of the cat. J Physiol353:463504.[Abstract]
Martinez LM, Reid RC, Alonso JM, Hirsch JA (1998) The role of excitation and inhibition in the orientation tuning of simple and complex cells in cat striate cortex. Soc Neurosci Abstr 24:1048.
Martinez LM, Reid RC, Alonso JM, Hirsch JA (1999) The synaptic structure of the simple receptive field. Soc Neurosci Abstr 25:1048.
Martinez LM, Alonso JM, Reid RC, Hirsch JA (2002) Laminar processing of stimulus orientation in cat visual cortex. J Physiol 540:321333.
Moore CI, Nelson SB (1998) Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J Neurophysiol 80:28822892.
Movshon JA, Thompson ID, Tolhurst DJ (1978a) Spatial summation in the receptive fields of simple cells in the cats striate cortex. J Physiol 283:5377.[Abstract]
Movshon JA, Thompson ID, Tolhurst DJ (1978b) Receptive field organization of complex cells in the cats striate cortex. J Physiol 283:7999.[Abstract]
Palmer LA, Davis TL (1981) Receptive-field structure in cat striate cortex. J Neurophysiol 46:260276.
Pare D, Shink E, Gaudreau H, Destexhe A, Lang EJ (1998) Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons In vivo. J Neurophysiol 79:14501460.
Reid RC, Alonso JM (1995) Specificity of monosynaptic connections from thalamus to visual cortex. Nature 378:281284.[CrossRef][ISI][Medline]
Ringach DL, Hawkan MJ, Shapley R (1997) Dynamics of orientation tuning in macaque primary visual cortex. Nature 387:281284.[CrossRef][ISI][Medline]
Shapley R, Lennie P (1985) Spatial frequency analysis in the visual system. Annu Rev Neurosci 8:547583.[CrossRef][ISI][Medline]
Sherman SM, Guillery RW (2001) Exploring the thalamus. San Diego, CA: Academic Press.
Sillito AM (1985) Inhibitory circuits and orientation selectivity in the visual cortex. In: Models of the visual cortex (Rose D, Dobson VG, eds), pp. 396407. New York: Wiley.
Skottun BC, De Valois RL, Grosof DH, Movshon JA, Albrecht DG, Bonds AB (1991) Classifying simple and complex cells on the basis of response modulation. Vision Res 31:10791086.[CrossRef][ISI][Medline]
Somers DC, Nelson SB, Sur M (1995) An emergent model of orientation selectivity in cat visual cortical simple cells. J Neurosci 15:54485465.[Abstract]
Sompolinsky H, Shapley RM (1997) New perspectives on the mechanisms for orientation selectivity. Curr Opin Neurobiol 7:515522.
Stratford KJ, Tarczy-Hornoch K, Martin KA, Bannister NJ, Jack JJ (1996) Excitatory synaptic inputs to spiny stellate cells in cat visual cortex. Nature 382:258261.[CrossRef][ISI][Medline]
Swadlow HA, Gusev AG (2000) The influence of single VB thalamo-cortical impulses on barrel columns of rabbit somatosensory cortex. J Neurophysiol 83:28022813.
Szulborski RG, Palmer LA (1990) The two-dimensional spatial structure of nonlinear subunits in the receptive fields of complex cells. Vision Res 30:249254.[CrossRef][ISI][Medline]
Tanaka K (1983) Cross-correlation analysis of geniculostriate neuronal relationships in cats. J Neurophysiol 49:13031318.
Tolhurst DJ, Dean AF (1987) Spatial summation by simple cells in the striate cortex of the cat. Exp Brain Res 66:607620.[CrossRef][ISI][Medline]
Troyer TW, Krukowski AE, Priebe NJ, Miller KD (1998) Contrast-invariant orientation tuning in cat visual cortex: thalamocortical input tuning and correlation-based intracortical connectivity. J Neurosci 18:59085927.
Usrey WM, Reppas JB, Reid RC (1999) Specificity and strength of retinogeniculate connections. J Neurophysiol 82:35273540.
Usrey WM, Alonso JM, Reid RC (2000) Synaptic interactions between thalamic inputs to simple cells in cat visual cortex. J Neurosci 20:54615467.
Volgushev M, Pei X, Vidyasagar TR, Creutzfeldt OD (1993) Excitation and inhibition in orientation selectivity of cat visual cortex neurons
Wielaard DJ, Shelley M, McLaughlin D, Shapley R (2001) How simple cells are made in a nonlinear network model of the visual cortex. J Neurosci 21:52035211.
Wolfe J, Palmer LA (1998) Temporal diversity in the lateral geniculate nucleus of cat. Vis Neurosci 15:653675.[CrossRef][ISI][Medline]
Zhu JJ, Connors BW (1999) Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. J Neurophysiol 81:11711183.