Models and measurements of functional maps in v1.
Issa NP, Rosenberg A, Husson TR. J Neurophysiol.
2008 99:2745-2754. Full
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
Atul K. Mallik, T. Robert Husson, Jing X. Zhang,
Ari Rosenberg, Naoum P. Issa. Vision Research. 2008, 48:1545-1553.
Full text (pdf).
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
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
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
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
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
Husson TR, Mallik AK, Zhang JX, Issa NP. J Neurosci.
2007 ;27:8665-8675. Full
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.
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
Inhibitory circuits in sensory maps develop through excitation.
N.P. Issa Trends Neurosci. 2003 26:456-458. Full
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
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
Spatial frequency maps in cat visual cortex.
Issa NP, Trepel C, Stryker MP. J Neurosci. 2000 20:8504-8514. Full
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
Issa NP, Trachtenberg JT, Chapman B, Zahs KR, Stryker MP.
J Neurosci. 1999 Aug 15;19(16):6965-78. Full
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
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
Silver MA, Fagiolini M, Gillespie DC, Howe CL, Frank MG, Issa NP, Antonini
A, Stryker MP. Neuroscience. 2001;108(4):569-85. Full
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.
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.
Hair-bundle stiffness dominates the elastic reactance to otolithic-membrane
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.
list of publications for N.P. Issa
T.I. Baker and N.P. Issa. SFN 2004. Separable Cortical
Maps Underlie the Population Responses to Complex Visual Stimuli. Full
J. Zhang and N.P. Issa. SFN 2004. Dynamic Visual
Acuity and Activation Patterns of Spatial Frequency Domains of Primary
Visual Cortex. Full