Issa Lab Home

Research Interests







Models and measurements of functional maps in v1.

Issa NP, Rosenberg A, Husson TR. J Neurophysiol. 2008 99:2745-2754. Full text (pdf).
The organization of primary visual cortex has been heavily studied for nearly 50 years, and in the last 20 years functional imaging has provided high-resolution maps of its tangential organization. Recently, however, the usefulness of maps like those of orientation and spatial frequency (SF) preference has been called into question because they do not, by themselves, predict how moving images are represented in V1. In this review, we discuss a model for cortical responses (the spatiotemporal filtering model) that specifies the types of cortical maps needed to predict distributed activity within V1. We then review the structure and interrelationships of several of these maps, including those of orientation, SF, and temporal frequency preference. Finally, we discuss tests of the model and the sufficiency of the requisite maps in predicting distributed cortical responses. Although the spatiotemporal filtering model does not account for all responses within V1, it does, with reasonable accuracy, predict population responses to a variety of complex stimuli.

The organization of spatial frequency maps measured by cortical flavoprotein autofluorescence.

Atul K. Mallik, T. Robert Husson, Jing X. Zhang, Ari Rosenberg, Naoum P. Issa. Vision Research. 2008, 48:1545-1553. Full text (pdf).
To determine the organization of spatial frequency (SF) preference within cat Area 17, we imaged responses to stimuli with different SFs using optical intrinsic signals (ISI) and flavoprotein autofluorescence (AFI). Previous studies have suggested that neurons cluster based on SF preference, but a recent report argued that SF maps measured with ISI were artifacts of the vascular bed. Because AFI derives from a non-hemodynamic signal, it is less contaminated by vasculature. The two independent imaging methods produced similar SF preference maps in the same animals, suggesting that the patchy organization of SF preference is a genuine feature of Area 17.

Glomerular activation patterns and the perception of odor mixtures.

Grossman KJ, Mallik AK, Ross J, Kay LM, Issa NP. Eur J Neurosci. 2008, 27:2676-2685. Full text (pdf).
Odor mixtures can produce several qualitatively different percepts; it is not known at which stage of processing these are determined. We asked if activity within the first stage of olfactory processing, the glomerular layer of the olfactory bulb, predicts odor mixture perception. We characterized how mice respond to components after training to five different mixture ratios of pentanal and hexanal, and found two types of responses: elemental perception and overshadowing. We then used intrinsic signal imaging to observe glomerular activity in response to the same mixtures and their components. As has been previously described, glomerular activity patterns produced by mixtures resemble the linear combination of responses to components. Mice trained to identify mixtures with more hexanal than pentanal recognized hexanal but not pentanal when the odorants were presented alone (overshadowing). Consistent with these behavioral responses, the imaged activity pattern in response to mixtures was similar to that produced to hexanal alone. Moreover, there was no significant effect of glomerular inhibition in the imaged response. In contrast, the glomerular activity patterns did not predict elemental perception: when trained to identify mixtures with more pentanal than hexanal, mice recognized both components equally well, even with highly overlapping activation patterns. This suggests that spatial activity patterns within the olfactory bulb are not always sufficient to specify component recognition in mixtures.

The representation of complex images in spatial frequency domains of primary visual cortex.

Zhang, J.X., Rosenberg, A., Mallik, A.K., Husson, T.R., Issa, N.P. J. Neurosci. 2007, 27:9310-9308. Full text (pdf).
The organization of cat primary visual cortex has been well mapped using simple stimuli such as sinusoidal gratings, revealing superimposed maps of orientation and spatial frequency preferences. However, it is not yet understood how complex images are represented across these maps. In this study, we ask whether a linear filter model can explain how cortical spatial frequency domains are activated by complex images. The model assumes that the response to a stimulus at any point on the cortical surface can be predicted by its individual orientation, spatial frequency, and temporal frequency tuning curves. To test this model, we imaged the pattern of activity within cat area 17 in response to stimuli composed of multiple spatial frequencies. Consistent with the predictions of the model, the stimuli activated low and high spatial frequency domains differently: at low stimulus drift speeds, both domains were strongly activated, but activity fell off in high spatial frequency domains as drift speed increased. To determine whether the filter model quantitatively predicted the activity patterns, we measured the spatiotemporal tuning properties of the functional domains in vivo and calculated expected response amplitudes from the model. The model accurately predicted cortical response patterns for two types of complex stimuli drifting at a variety of speeds. These results suggest that the distributed activity of primary visual cortex can be predicted from cortical maps like those of orientation and SF preference generated using simple, sinusoidal stimuli, and that dynamic visual acuity is degraded at or before the level of area 17.

Functional imaging of primary visual cortex using flavoprotein autofluorescence

Husson TR, Mallik AK, Zhang JX, Issa NP. J Neurosci. 2007 ;27:8665-8675. Full text (pdf).
Neuronal autofluorescence, which results from the oxidation of flavoproteins in the electron transport chain, has recently been used to map cortical responses to sensory stimuli. This approach could represent a substantial improvement over other optical imaging methods because it is a direct (i.e., nonhemodynamic) measure of neuronal metabolism. However, its application to functional imaging has been limited because strong responses have been reported only in rodents. In this study, we demonstrate that autofluorescence imaging (AFI) can be used to map the functional organization of primary visual cortex in both mouse and cat. In cat area 17, orientation preference maps generated by AFI had the classic pinwheel structure and matched those generated by intrinsic signal imaging in the same imaged field. The spatiotemporal profile of the autofluorescence signal had several advantages over intrinsic signal imaging, including spatially restricted fluorescence throughout its response duration, reduced susceptibility to vascular artifacts, an improved spatial response profile, and a faster time course. These results indicate that AFI is a robust and useful measure of large-scale cortical activity patterns in visual mammals.

Cortical maps of separable tuning properties predict population responses to complex visual stimuli

Baker TI, Issa NP. J Neurophysiol. 2005 94:775-787. Full text (pdf).
In the earliest cortical stages of visual processing, a scene is represented in different functional domains selective for specific features. Maps of orientation and spatial frequency preference have been described in the primary visual cortex using simple sinusoidal grating stimuli. However, recent imaging experiments suggest that the maps of these two spatial parameters are not sufficient to describe patterns of activity in different orientation domains generated in response to complex, moving stimuli. A model of cortical organization is presented in which cortical temporal frequency tuning is superimposed on the maps of orientation and spatial frequency tuning. The maps of these three tuning properties are sufficient to describe the activity in orientation domains that have been measured in response to drifting complex images. The model also makes specific predictions about how moving images are represented in different spatial frequency domains. These results suggest that the tangential organization of primary visual cortex can be described by a set of maps of separable neuronal receptive field features including maps of orientation, spatial frequency, and temporal frequency tuning properties.

Inhibitory circuits in sensory maps develop through excitation.

    N.P. Issa Trends Neurosci. 2003 26:456-458. Full text (pdf).
    Inhibitory and excitatory connections are equal partners in determining neuronal response properties. Although the development and plasticity of excitatory networks have been heavily studied, little is known about how inhibitory circuits develop. In a recent study, Gunsoo Kim and Karl Kandler have shown that, as in the development of excitatory circuits, synapse elimination and strengthening are important processes for the development of well-organized inhibitory circuits.

Sleep enhances plasticity in the developing visual cortex.

    Frank MG, Issa NP, Stryker MP. Neuron. 2001 30:275-287. Full text (PDF).
    During a critical period of brain development, occluding the vision of one eye causes a rapid remodeling of the visual cortex and its inputs. Sleep has been linked to other processes thought to depend on synaptic remodeling, but a role for sleep in this form of cortical plasticity has not been demonstrated. We found that sleep enhanced the effects of a preceding period of monocular deprivation on visual cortical responses, but wakefulness in complete darkness did not do so. The enhancement of plasticity by sleep was at least as great as that produced by an equal amount of additional deprivation. These findings demonstrate that sleep and sleep loss modify experience-dependent cortical plasticity in vivo. They suggest that sleep in early life may play a crucial role in brain development.

Spatial frequency maps in cat visual cortex.

    Issa NP, Trepel C, Stryker MP. J Neurosci. 2000 20:8504-8514. Full text (PDF).
    Neurons in the primary visual cortex (V1) respond preferentially to stimuli with distinct orientations and spatial frequencies. Although the organization of orientation selectivity has been thoroughly described, the arrangement of spatial frequency (SF) preference in V1 is controversial. Several layouts have been suggested, including laminar, columnar, clustered, pinwheel, and binary (high and low SF domains). We have reexamined the cortical organization of SF preference by imaging intrinsic cortical signals induced by stimuli of various orientations and SFs. SF preference maps, produced from optimally oriented stimuli, were verified using targeted microelectrode recordings. We found that a wide range of SFs is represented independently and mostly continuously within V1. Domains with SF preferences at the extremes of the SF continuum were separated by no more than (3/4) mm (conforming to the hypercolumn description of cortical organization) and were often found at pinwheel center singularities in the cortical map of orientation preference. The organization of cortical maps permits nearly all combinations of orientation and SF preference to be represented in V1, and the overall arrangement of SF preference in V1 suggests that SF-specific adaptation effects, found in psychophysical experiments, may be explained by local interactions within a given SF domain. By reanalyzing our data using a different definition of SF preference than is used in electrophysiological and psychophysical studies, we can reproduce the different SF organizations suggested by earlier studies.

The critical period for ocular dominance plasticity in the Ferret's visual cortex.

    Issa NP, Trachtenberg JT, Chapman B, Zahs KR, Stryker MP.
    J Neurosci. 1999 Aug 15;19(16):6965-78. Full text (PDF).
    Microelectrode recordings and optical imaging of intrinsic signals were used to define the critical period for susceptibility to monocular deprivation (MD) in the primary visual cortex of the ferret. Ferrets were monocularly deprived for 2, 7 or >14 d, beginning between postnatal day 19 (P19) and P110. The responses of visual cortical neurons to stimulation of the two eyes were used to gauge the onset, peak, and decline of the critical period. MDs ending before P32 produced little or no loss of response to the deprived eye. MDs of 7 d or more beginning around P42 produced the greatest effects. A rapid decline in cortical susceptibility to MD was observed after the seventh week of life, such that MDs beginning between P50 and P65 were approximately half as effective as those beginning on P42; MDs beginning after P100 did not reduce the response to the deprived eye below that to the nondeprived eye. At all ages, 2 d deprivations were 55-85% as effective as 7 d of MD. Maps of intrinsic optical responses from the deprived eye were weaker and less well tuned for orientation than those from the nondeprived eye, with the weakest maps seen in the hemisphere ipsilateral to the deprived eye. Analysis of the effects of 7 d and longer deprivations revealed a second period of plasticity in cortical responses in which MD induced an effect like that of strabismus. After P70, MD caused a marked loss of binocular responses with little or no overall loss of response to the deprived eye. The critical period measured here is compared to other features of development in ferret and cat.

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development.

    Silver MA, Fagiolini M, Gillespie DC, Howe CL, Frank MG, Issa NP, Antonini A, Stryker MP. Neuroscience. 2001;108(4):569-85. Full text (PDF).

The entry and clearance of Ca2+ at individual presynaptic active zones of hair cells from the bullfrog's sacculus.

    Issa NP, Hudspeth AJ. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9527-32. Full text (PDF).

Characterization of fluo-3 labelling of dense bodies at the hair cell's presynaptic active zone.

    Issa NP, Hudspeth AJ. J Neurocytol. 1996 Apr;25(4):257-66.

Confocal-microscopic visualization of membrane addition during synaptic exocytosis at presynaptic active zones of hair cells.

    Hudspeth AJ, Issa NP. Cold Spring Harb Symp Quant Biol. 1996;61:303-7.

Clustering of Ca2+ channels and Ca(2+)-activated K+ channels at fluorescently labeled presynaptic active zones of hair cells.

    Issa NP, Hudspeth AJ. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7578-82. Full text (PDF).

Hair-bundle stiffness dominates the elastic reactance to otolithic-membrane shear.

    Benser ME, Issa NP, Hudspeth AJ. Hear Res. 1993 Aug;68(2):243-52.

From U sequence to Farey sequence: A unification of one-parameter scenarios.

    Ringland J, Issa N, Schell M. Physical Review. A. 1990 Apr 15;41(8):4223-4235. Full text (PDF).

PubMed list of publications for N.P. Issa

Recent Posters

    T.I. Baker and N.P. Issa. SFN 2004. Separable Cortical Maps Underlie the Population Responses to Complex Visual Stimuli. Full Poster (PDF)

    J. Zhang and N.P. Issa. SFN 2004. Dynamic Visual Acuity and Activation Patterns of Spatial Frequency Domains of Primary Visual Cortex. Full Poster (PDF)