DISCUSSION
These results show that multisensory neurons are present in ferret PPr
cortex at developmental stages that precede sexual maturity
(<~P120). Designated as the “infant” period,
multisensory neurons at that time, however, were the minority of neurons
observed and only one showed MSI (which was the singular subthreshold
neuron identified in this age group). At this early developmental stage,
these data from infant, pre-pubertal ferrets closely resemble findings
in cat cortex (Wallace et al. , 2006), as well as superior
colliculus (Wallace & Stein, 1997), where early multisensory neurons
respond independently to stimulation from more than one sensory modality
but fail to integrate responses when those cues are presented together.
Thus, despite the presence of multisensory convergence, the capacity to
integrate multisensory responses apparently is not yet developed in such
young cats or ferrets.
For the series of older ferrets (e.g., >P120), the presence
of multisensory neurons progressively increased, as was also seen in
developing cats following the epoch in which the first multisensory
neurons appeared (Wallace et al. , 2006). In the present study,
this period is referred to as “adolescence” because, like
post-pubertal humans, neural development continues beyond the age of
sexual maturity. It is well known that neural maturity in humans is
delayed for approximately a decade after sexual onset, especially for
higher-order regions, such as inferior parietal and frontal cortices
(Spear, 2000a; Spear, 2000b). To our knowledge such conditions have not
yet been identified in ferrets (or cats) and hence, there is ambiguity
in what is actually defined as being neurally adult in these animals.
Indeed, the study of multisensory development in cats did not define
neural adulthood, except that the cats designated as adults were older
than P180, which is the age of sexual maturity for cats. As a
consequence, all the developmental age groups studied in cats were
pre-pubertal (Wallace et al. , 2006). In contrast, the ferret age
groups in which MSI appeared and developed in bimodal neurons were all
post-pubertal adolescents. These conflicting results may be accounted
for by the species and methodological differences between these studies,
but it might also be possible that PPr neurons mature more slowly than
those of the AES perhaps as a reflection of cortical hierarchical
differences.
Further evidence that multisensory changes occur in PPr during the
ferret adolescent stages comes from the observation that multisensory
integration increases in magnitude after the age of sexual maturity at
~P120. Figure 2B summarizes this feature for bimodal
neurons that exhibit MSI, and significant increases in multisensory
enhancement were demonstrated for stages of adolescence at ages P160-200
and P200-240. Similar developmental increases in multisensory
enhancement have also been reported in another study of PPr neurons in
early alcohol-treated and control ferrets (Keum et al. , 2023).
However, these data do not mirror the MSI levels reported for cats,
where the magnitude of multisensory response change observed during
development was not different from that seen in adults (Wallace et
al. , 2006). It seems possible that these differences in results may be
accounted for by the species, regional and methodological differences of
these studies.
The present study also examined the levels of multisensory response
change that were not significantly different from the most effective
unisensory stimulus. It must be kept in mind that these non-integrative
responses were evoked in bimodal neurons that were individually
activated by visual and by somatosensory stimulation. As a consequence,
both stimuli were effective when presented alone and, by definition,
were presented within their excitatory receptive fields. Thus, the
observed non-integrative effects could not have been induced by
inhibitory effects of one stimulus being presented outside of its
receptive field. Numerous reports have documented and examined
non-integrated multisensory responses in bimodal neurons in a variety of
neural areas (Perrault Jr et al. , 2005; Meredith et al. ,
2021; Merrikhi et al. , 2022a; Merrikhi et al. , 2022b). The
present study shows that such non-integrative multisensory effects were
strongly influenced by development because, as depicted in Figure 5D,
significant shifts were seen from primarily suppressive levels in
infants to progressively higher levels of multisensory response change
across the periods of adolescence. Furthermore, similar developmental
shifts in non-integrative responses were observed a separate study of
PPr neurons (Keum et al. , 2023). Ultimately, the present results
show that both non-integrative and integrative response modes of bimodal
neurons change during post-pubertal development.
We also examined the subthreshold form of multisensory neuron across the
different age groups. Although small in occurrence (as also observed in
other areas – (Meredith et al. , 2021; Merrikhi et al. ,
2022a; Merrikhi et al. , 2022b), their proportions showed an
increasing trend during development but no developmental pattern for
changes in MSI levels were demonstrated. A similarly low incidence of
multisensory response depression revealed the presence of the effect
during development, but consistent changes across development could not
be assessed.
In summary, the present study in ferret cortical area PPr identified
patterns of appearance of multisensory neurons during development that
were similar to those reported for cat cortex (Wallace et al. ,
2006). However, unlike the cat AES regions, the magnitude of MSI in
ferret PPr significantly increased across the post-pubertal
developmental stages. Furthermore, bimodal neurons whose multisensory
responses were not integrated showed a consistent shift from suppression
in infants to progressively higher levels of multisensory response chage
at the adolescent stages. These data, combined with the small presence
of subthreshold multisensory neurons give insight into how the
population of PPr neurons changes their responses to multisensory cues
across pre- and post-pubertal development. How these changes,
particularly during adolescence, are parlayed into the behavioral and
perceptual tasks of the region are clearly a topic for future
investigation.
ACKNOWLEDGMENTS:
Grant sponsor: National Institutes of Health; Grant number: NS064675
(MAM); AA13023 (AEM).