Introduction
How the cerebral cortex organizes itself to analyze and perceive the
sensory world around it has been the topic of intense scrutiny for
decades now (e.g., see (Crain, 1952; Grossman, 1955; Eayrs & Goodhead,
1959). In general, the course of neural sensory development has been
extensively examined from a unisensory perspective by evaluating
neuronal responses evoked by the presentation of stimuli from one
sensory modality. For example, development of cortical sensory responses
have been described for visual (Wiesel & Hubel, 1963), somatosensory
(Rubel, 1971) and auditory (Kral et al. , 2001) areas in a variety
of mammalian models from mice to non-human primates. From these and
numerous other studies, the general pattern of cortical sensory
development indicates that early postnatal responses are often
comparatively weak, with long response latencies, higher levels of
spontaneous activity and broad receptive fields regardless of the
modality involved. These features were found to progressively change
across postnatal development to eventually reach values consistent with
neurally mature adults. However, the brain does not habitate a
unisensory world and events commonly occur that are detected by more
than one sensory modality. Correspondingly, multisensory neurons have
been identified so frequently that it has been asserted that the
neocortex is “essentially multisensory” (Ghazanfar & Schroeder,
2006).
Despite the ubiquitous presence of cortical multisensory neurons, few
studies of the development of cortical neuronal multisensory properties
have been published. A very early study of multisensory development
observed neurons in feline association (Lateral Suprasylvian area)
cortex that primarily responded unisensory stimulation early in the
postnatal period (e.g., 67% at postnatal day 8), but were largely
replaced by multisensory neurons (89%) by postnatal day (P) 50 (Mayerset al. , 1971). This general multisensory developmental sequence
was reiterated for a different feline cortical region, the Anterior
Ectosylvian Sulcal cortex (AES), in a study by (Wallace et al. ,
2006). Here, the functional onset for somatosensory responsivity was
present for the earliest age group (P28), auditory onset occurred near
P56 and the onset of the first multisensory neurons (bimodal
somatosensory-auditory) was also seen at that same time. Further, visual
response activity was first observed at P84 at which time the first
multisensory neurons with visual inputs were also identified. Thus,
although unisensory neurons had earlier functional onsets than did
multisensory ones, it seemed that once a particular modality became
active, its functional effect applied to both unisensory and
multisensory neurons. Furthermore, the time course of these respective
sensory onsets corresponded with the expression of specific sensory
guided behaviors (Larson & Stein, 1984). The Wallace et al. (2006)
study went even further to examine the development of multisensory
integration (MSI), which is the effect that multisensory neurons can
generate when responding to concurrent stimulation from more than one
sensory modality. Even though bimodal neurons were identified by P56,
neurons that exhibited MSI were not observed until P84, after which
their incidence progressively increased into adulthood. However, the
magnitude of MSI response change did not change across this
developmental period, since the levels observed at early stages (e.g.,
P84) were essentially the same as those seen in adults. Thus, this study
(Wallace et al. , 2006) revealed that multisensory features
develop gradually during maturation, but when they do they immediately
exhibited adult-like properties.
More recently, an additional form of multisensory neuron has been
identified that is different from the traditional bimodal (and trimodal)
types. This form, which responds to a single unisensory stimulus, but
has that response significantly modified by the presence of a stimulus
from a different modality, is termed a subthreshold multisensory neuron
(Dehner et al. , 2004; Allman & Meredith, 2007; Allman et
al. , 2009). Like bimodal neurons, subthreshold multisensory neurons can
show multisensory response enhancement (as studied in (Wallace et
al. , 2006)) as well as response depression (Dehner et al. ,
2004). However, it is not known when these subthreshold multisensory
neurons occur developmentally nor has the developmental time-course of
multisensory response depression been reported. In addition,
multisensory neurons can respond to multisensory stimulation without
exhibiting MSI, but with responses that fail to achieve a statistically
significant difference from their most effective unisensory response
(e.g., see (Perrault Jr et al. , 2005)). Such non-significant
response changes, however, can contribute to substantial effects at the
population level (Merrikhi et al. , 2022a; Merrikhi et al. ,
2022b) although their developmental presentation is not known.
Furthermore, the AES area is a conglomerate region consisting of 3
different sensory representations, each with their own connectional
features and functional properties (for review, see (Meredith et
al. , 2018)). Consequently, the developmental effects for a singular
multisensory cortical region, to our knowledge, has not yet been
described. Therefore, the present investigation seeks to incorporate
these recent details about multisensory processing into an assessment of
the development of multisensory processing within a singular cortical
region, the ferret Rostral Posterior Parietal cortex (PPr).
Like many higher mammals, ferrets have a gyrencephalic brain,
demonstrate a high proportion of white matter (Schwerin et al. ,
2017), and their visual cortices exhibit ocular and
orientation-selectively columns (Issa et al. , 1999; Medinaet al. , 2005). As a consequence, ferrets have been used to
examine amblyopia (Liao et al. , 2004; Krahe et al. , 2005)
or crossmodal plasticity (Roe et al. , 1990) as well as in
neuropsychiatric and neurologic conditions such as Fetal Alcohol
Spectrum Disorders (Medina et al. , 2003; Medina et al. ,
2005; 2006; Paul et al. , 2010; Keum et al. , 2023), TBI
(Schwerin et al. , 2017; Goodfellow et al. , 2022) and
cortical dysplasia (Noctor et al. , 1999; Abbah & Juliano, 2014).
The cortical location of the PPr is depicted on the lateral view of the
ferret brain shown in Figure 1A. This region has been demonstrated to
contain unisensory somatosensory and unisensory visual neurons, as well
as bimodal and subthreshold multisensory neurons affected by those same
sensory modalities (Manger et al. , 2002; Foxworthy et al. ,
2013; Foxworthy et al. , 2014). The receptive fields of these
neurons are comparatively large, such that a standardized stimulus set
is effective in activating a large proportion of sensory neurons within
a multiple single-unit recording site. In addition to ferrets, the
parietal cortex is well studied in humans, monkeys and rodents and
behavioral involvements have been established for the region in relation
to attention, rectification of spatial maps, goal-directed behaviors and
self-awareness (Calton & Taube, 2009; Nitz, 2009; Reep & Corwin, 2009;
Save & Poucet, 2009; Alais et al. , 2010; Kaas et al. ,
2011; Blanke, 2012). Because all eutherians studied reveal a
multisensory visual–somatosensory region between visual and
somatosensory cortical representations (Manger et al. , 2002;
Kaas, 2009), the properties of bimodal and unisensory neurons observed
in the ferret PPr can be generalizable to a wide number of species.