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.