Department of Neurobiology and Anatomy, Wake Forest University
School of Medicine, Winston-Salem, North Carolina 27157
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INTRODUCTION |
The ability to respond to stimuli from different
sensory modalities, and the ability to integrate the information from
these different modalities, are characteristic properties of neurons in
the superior colliculus (SC) (see Stein and Meredith
1993
). Each multisensory SC neuron has multiple receptive
fields that are in spatial register. As a consequence of this
organization, multiple sensory stimuli (e.g., visual and auditory)
originating from the same event will fall within the overlapping
receptive fields of the same neuron, resulting in a substantially
enhanced response (Meredith and Stein 1996
). If,
however, one of those stimuli is outside its receptive field, it can
inhibit the neuron's responses to the other stimulus (Kadunce
et al. 1997
). In a parallel manner, overt orientation and
approach behaviors are facilitated by spatially coincident
visual-auditory stimulus combinations, and depressed when these stimuli
are spatially disparate (Stein et al. 1989
).
Recently, however, it has been shown that multisensory integration is
not an obligatory property of these neurons. In the adult, reversible
deactivation of a region of association cortex, the cortex surrounding
the anterior ectosylvian sulcus (AES), compromises the multisensory
integrative capabilities of SC neurons (Wallace and Stein
1994
) and the multisensory behaviors on which they depend
(Wilkinson et al. 1996
). Furthermore, early in life the
responses of neonatal multisensory SC neurons to combinations of cues
from different modalities typically are no different from their
responses to those cues when presented individually (Wallace and
Stein 1997
). Thus the present study was initiated to determine if, as postulated (see Wallace and Stein 1997
), the
appearance of SC multisensory integration reflects the development of
corticotectal influences, and, if so, what maturational changes these
influences undergo.
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METHODS |
Procedures were conducted in accordance with the guidelines
established by the Institutional Animal Care and Use Committee of Wake
Forest University, are identical to those previously reported (Wallace and Stein 1994
, 1997
), and will
be described only briefly. In anesthetized animals, multisensory SC
neurons were isolated using extracellular recording techniques. The
neuron's receptive fields were mapped and its modality-specific and
multisensory response profiles were quantitatively determined. The
location, timing, and physical characteristics of the stimuli were
varied in an effort to maximize multisensory response enhancement. The criterion for multisensory integration was a statistically significant (paired t-test) increase in the number of impulses evoked by
a cross-modal stimulus combination (e.g., visual-auditory) over that
evoked by the most effective ("dominant") modality-specific stimulus. When this criterion was reached, the magnitude of the resultant interaction for each neuron was calculated using the formula
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|
where CM is the combined modality response and
SMmax is the response to the most effective
single modality. Modality-specific and multisensory responses were
recorded before, during, and after cortical deactivation by
cryoblockade (e.g., Wallace and Stein 1994
). A
deactivation-induced effect was a significant (t-test) decline in multisensory enhancement. Only cases in which
postdeactivation responses returned to within 20% of control levels
were considered for further analysis.
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RESULTS |
The responses of multisensory SC neurons (n = 104)
were quantitatively examined in 37 neonatal animals ranging in age from 1-135 days postnatal (dpn). These data were compared with an adult data set (n = 78) previously collected (Wallace
and Stein 1994
). Prior to 28 dpn, multisensory SC neurons
(n = 15) failed to exhibit multisensory integration and
in all but 2 cases their responses were unaffected by AES deactivation.
The first neuron exhibiting multisensory integration was encountered at
28 dpn, and AES deactivation eliminated the neuron's enhanced
multisensory response without significantly affecting its
modality-specific responses. This selectivity of AES deactivation for
multisensory enhancement proved to be characteristic, with only 15/104
(14%) of the neurons examined showing effects on modality-specific responses. In this small group of neurons, these effects averaged a
28% reduction in one of the two modality-specific responses. These
modality-specific effects did not change in either incidence or
magnitude during development, were equivalent for integrating and
nonintegrating neurons and, as in the adult cat (Jiang et al.
1999
), were not predictive of any AES
deactivation-induced changes in multisensory responses. As development
progressed, the proportion of integrating multisensory neurons grew;
these neurons were almost invariably affected by AES deactivation, and they were often found in clusters (Fig.
1).

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Fig. 1.
Multisensory integrative and multisensory nonintegrative neurons were
often located in nearby clusters. Top: the two
neighboring visual-auditory neurons recorded in this 35 dpn animal
shown on the left schematic of a coronal section through the superior
colliculus (SC) failed to integrate cross-modal cues
( ), whereas the three shown on the penetration on the
right did ( ). Middle: receptive fields
and stimulus locations for a representative neuron from each
penetration are shown on a schematic of visual and auditory space.
Bottom: rasters, peristimulus histograms, and summary
bar graphs depict the modality-specific (V, A) and multisensory (VA)
responses of these neurons under three conditions: prior to anterior
ectosylvian sulcus (AES) deactivation (control 1), during AES
deactivation, and after reactivation (control 2). Whereas in the
nonintegrative neuron (left), AES deactivation had no
effect, in the integrative neuron (right), multisensory
integration was eliminated by AES deactivation. * P < 0.05, ** P < 0.01.
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Interestingly, AES deactivation effects on the youngest multisensory
integrative neurons were comparable to those found in adults
(Wallace and Stein 1994
; Jiang et al.
1999
). Thus despite a steady developmental increase in the
incidence of neurons exhibiting adult-like multisensory integration
(Fig. 2), neither the magnitude of their
multisensory response enhancement nor the magnitude of the effect of
AES deactivation showed any age-dependent changes. Such a result
suggests that for any given SC neuron, the functional AES link was
established abruptly, so that the neuron was immediately rendered
capable of adult-like multisensory integration (Fig. 2). That this
functional transition was attributable to the onset of an AES-SC
functional link was also consistent with the observation that AES
deactivation eliminated the differences between the multisensory responses of the populations of integrative and nonintegrative neurons
(Fig. 3).

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Fig. 2.
The proportion of multisensory integrative SC neurons increased during
postnatal development, and the vast majority of these neurons had their
multisensory integrative capabilities abolished by AES deactivation.
Numbers in parentheses show the number of multisensory neurons tested
for cortical deactivation-induced effects. The bar graphs represent
pooled data from 4 age groups and show that regardless of age,
multisensory integrative neurons exhibited similar multisensory
response enhancements (control) and were similarly affected by AES
deactivation.
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Fig. 3.
Nonintegrative and integrative multisensory neurons differed in their
reactions to AES deactivation. Left: the multisensory
responses of the population of nonintegrating neonatal neurons (pooled
over age) is plotted as a function of their dominant modality-specific
responses before ( ) and during ( ) AES
deactivation. Note that the best fit to the data showed that there was
no significant difference between the multisensory response of these
neurons and their dominant modality-specific response (gray line,
unity; ANOVA, F = 1.73, P > 0.05), and that AES deactivation had no significant effect on their
responses (repeated measures ANOVA, F = 2.34, P > 0.05). Inset shows that the
multisensory response was significantly less than the algebraic sum of
the two modality-specific responses (gray line) and that, once again,
AES deactivation had little effect on the response function.
Right: in contrast, the multisensory responses of
integrative neurons were significantly greater than their dominant
modality-specific response (ANOVA, F = 45.6, P < 0.01) and the sum of their modality-specific
responses (ANOVA, F = 12.6, P < 0.05). AES deactivation shifted these functions downward (repeated
measures ANOVA, F = 61.2, P < 0.001 for main graph; F = 68.7, P < 0.001 for inset), rendering
them indistinguishable from the functions for their nonintegrative
counterparts (ANCOVA, F = 1.93, P > 0.05 for main graph; F = 1.55, P > 0.05 for inset).
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DISCUSSION |
These observations suggest that the development of the SC from a
strictly modality-specific structure to a structure in which its
neurons can respond to (but not integrate) multiple sensory modalities
(see Stein et al. 1973
; Wallace and Stein
1997
) reflects the functional maturation of inputs from sources
other than AES. However, the transition from this nonintegrative
multisensory state to the adult integrative state appears to be
intimately tied to the functional maturation of inputs from AES. It is
not possible, in the absence of longitudinal recordings from the same neurons, to determine whether individual SC neurons pass through each
of these developmental phases. Nevertheless, this seems likely, and
provides a parsimonious explanation for why so many neonatal multisensory SC neurons fail to integrate cross-modal cues, but why so
few such neurons are encountered in adults (Wallace and Stein
1997
). Given that the incidence of recorded sensory neurons in
the SC differs little from about 6 wk to maturity, despite major
changes in the incidence of multisensory integrative neurons, there is
little support for the possibility that integrative multisensory neurons remain inactive until they become fully capable of integrating cross-modal information.
The strikingly selective effect of AES deactivation on multisensory
integration in neonatal SC neurons parallels the finding in adults, in
which the majority of SC neurons have been shown to depend on
influences from the AES for their multisensory integration capabilities
but not for their ability to respond to individual cues from different
modalities (Wallace and Stein 1994
; Jiang et al.
1999
). These observations support the hypothesis that the ontogeny of multisensory integration in the SC is, in large part, a
reflection of the maturational onset of corticotectal influences from
the AES (see Wallace and Stein 1997
). Moreover, the data suggest that this event takes place in an abrupt, or "gate-like," manner on any given SC neuron, and immediately provides that neuron with the capability to engage in multisensory integration. This helps
explain the findings that the magnitude of multisensory interactions
and the susceptibility of such interactions to AES deactivation remain
relatively constant during development. The apparent abrupt onset of
corticotectal influences from the AES onto multisensory (i.e., deep
layer) SC neurons is not without precedent, as there is also an abrupt
onset of corticotectal influences from primary visual cortex onto
superficial layer visual neurons (Stein and Gallagher
1981
). The small number of neonatal SC neurons that exhibited
multisensory integration and in which this integration was unaffected
by AES deactivation were likely dependent on influences from an
adjacent region of association cortex, the rostral lateral suprasylvian
cortex (Jiang et al. 1999
).
It is interesting to note that the AES, long considered an
"association" area, does indeed play an associative role and
appears to do so in two ways. It contains not only a substantial
population of multisensory neurons that can integrate their multiple
sensory inputs in much the same way as do SC neurons (Wallace et
al. 1992
; Jiang et al. 1994
), but also a
substantial number of corticotectal neurons (Stein et al.
1983
) that mediate multisensory integration in the SC
(Wallace and Stein 1994
). It is surprising to note that these represent independent circuits. Multisensory neurons in AES do
not project to the SC, whereas many of their modality-specific counterparts do (see Wallace et al. 1993
).
Although AES corticotectal projections are already identifiable in
newborn animals (McHaffie et al. 1988
), apparently they are not functional in animals younger than four postnatal weeks. While
little is known about the development of AES, the present data
demonstrate that the maturational course of its functional influences
on SC neurons corresponds well with the most sensitive period of
structural and functional modifications of primary sensory cortex
(e.g., Wiesel and Hubel 1965
; Daw et al.
1992
), a period that is essential to adapt cortex to the
specific features and meaning of the sensory cues encountered in the
animal's environment. Given that the responses of AES neurons are also
plastic (Rauschecker and Korte 1993
), it is intriguing
to consider the possibility that AES corticotectal influences over any
individual SC neuron are initiated only after these inputs are capable
of modulating SC processes and SC-mediated overt responses in an
adaptive fashion.
This research was supported by National Institute of Neurological
Disorders and Stroke Grants NS-22543 and NS-36916.
Address for reprint requests: M. T. Wallace, Dept. of Neurobiology
and Anatomy, Wake Forest University School of Medicine, Medical Center
Boulevard, Winston-Salem, NC 27157-1010.
The costs of publication of this article were defrayed in part
by the payment of page charges. The article must therefore be hereby
marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.