Cortical and thalamic connectivity of the auditory anterior ectosylvian cortex of early-deaf cats: Implications for neural mechanisms of crossmodal plasticity.

Early hearing loss leads to crossmodal plasticity in regions of the cerebrum that are dominated by acoustical processing in hearing subjects. Until recently, little has been known of the connectional basis of this phenomenon. One region whose crossmodal properties are well-established is the auditory field of the anterior ectosylvian sulcus (FAES) in the cat, where neurons are normally responsive to acoustic stimulation and its deactivation leads to the behavioral loss of accurate orienting toward auditory stimuli. However, in early-deaf cats, visual responsiveness predominates in the FAES and its deactivation blocks accurate orienting behavior toward visual stimuli. For such crossmodal reorganization to occur, it has been presumed that novel inputs or increased projections from non-auditory cortical areas must be generated, or that existing non-auditory connections were 'unmasked.' These possibilities were tested using tracer injections into the FAES of adult cats deafened early in life (and hearing controls), followed by light microscopy to localize retrogradely labeled neurons. Surprisingly, the distribution of cortical and thalamic afferents to the FAES was very similar among early-deaf and hearing animals. No new visual projection sources were identified and visual cortical connections to the FAES were comparable in projection proportions. These results support an alternate theory for the connectional basis for cross-modal plasticity that involves enhanced local branching of existing projection terminals that originate in non-auditory as well as auditory cortices.

Dendritic spine density in multisensory versus primary sensory cortex.

In sensory areas, neuronal dendritic spines receive sensory-specific inputs whose net activity drives neuronal spiking responses to effective external stimuli. Previous studies indicate that neurons in primary sensory cortical areas, which largely receive inputs from a single sensory modality, exhibit an average of 0.5-1.4 dendritic spines/µm, depending on species. In higher-order, associational cortices, inputs converge from multiple sensory sources onto individual, multisensory neurons. This raises the question: when inputs from two different modalities converge onto individual neurons, how are the dendritic spines apportioned to subserve the generation of robust spiking responses to each modality? As inputs arrive from two different sensory sources, it might be expected that neurons in multisensory areas exhibit approximately double the spine density of neurons in areas that receive just one sensory input. The present study examined this possibility in Golgi-stained neurons from ferret primary auditory (A1) and somatosensory (S1) cortices, as well as from regions in which inputs from two different sensory modalities converge: the lateral rostral suprasylvian sulcus (LRSS) and the rostral posterior parietal (PPr) areas. Dendritic spine density (spines/µm) was measured for pyramidal neurons in layers 2-3 and layers 5-6 for each cortical area from three animals using light microscopy. Primary sensory regions A1 and S1 showed remarkably similar average spine densities (A1 = 1.27 spines/µm ± 0.3 s.d.; S1 = 1.14 spines/µm ± 0.3), but average spine densities from the multisensory areas were lower (LRSS = 0.98 ± 0.3; PPr = 1.04 ± 0.3). Thus, for a given cortical area, dendritic spine density appears to be determined by factors other than the levels of sensory modality convergence.

Auditory influences on non-auditory cortices.

Although responses to auditory stimuli have been extensively examined in the well-known regions of auditory cortex, there are numerous reports of acoustic sensitivity in cortical areas that are dominated by other sensory modalities. Whether in 'polysensory' cortex or in visual or somatosensory regions, auditory responses in non-auditory cortex have been described largely in terms of auditory processing. This review takes a different perspective that auditory responses in non-auditory cortex, either through multisensory subthreshold or bimodal processing, provide subtle but consistent expansion of the range of activity of the dominant modality within a given area. Thus, the features of these acoustic responses may have more to do with the subtle adjustment of response gain within a given non-auditory region than the encoding of their tonal properties.

Crossmodal projections from somatosensory area SIV to the auditory field of the anterior ectosylvian sulcus (FAES) in Cat: further evidence for subthreshold forms of multisensory processing.

To date, evaluation of the neuronal basis for multisensory processing has focused on the convergence pattern that provides excitation from more than one sensory modality. However, a recent study (Dehner et al. in Cereb Cortex 14:387-401, 2004) has demonstrated excitatory-inhibitory multisensory effects that do not follow this conventional pattern and the present investigation documented a similar example of subthreshold cross-modal effects. Neuroanatomical tracers revealed that pyramidal neurons of the somatosensory area SIV project to the auditory field of the anterior ectosylvian sulcus (FAES), but subsequent electrophysiological tests showed that stimulation of SIV failed to elicit the expected orthodromic responses in FAES. Instead, combined auditory-SIV stimulation significantly suppressed FAES responses to auditory cues in approximately 25% of the neurons tested, and facilitated responses in another 5%. These modulatory responses in auditory FAES were similar in kind to those observed in somatosensory SIV and, as such, comprise further evidence for subthreshold forms of multisensory processing in cortex. Consequently, it seems likely that subthreshold cross-modal effects may impact other apparently 'unimodal' areas of the brain.

Cross-modal circuitry between auditory and somatosensory areas of the cat anterior ectosylvian sulcal cortex: a 'new' inhibitory form of multisensory convergence.

Examples of convergence of visual and auditory, or visual and somatosensory, inputs onto individual neurons abound throughout the brain, but substantially fewer incidences of auditory-somatosensory neurons have been reported. The present experiments sought to examine auditory-somatosensory convergence to assess whether there is a feature of this type of convergence that might obscure it from conventional methods of multisensory detection. Auditory-somatosensory convergence was explored in cat anterior ectosylvian sulcus (AES) cortex, where higher-order somatosensory area IV (SIV) and auditory field of the anterior ectosylvian sulcus (FAES) share a common border. While neuroanatomical tracers documented a projection from FAES to SIV, physiological studies failed to reveal the bimodal neurons expected from such cross-modal connectivity. Stimulation of FAES through indwelling electrodes also failed to excite any of the SIV neurons examined. However, when stimulation of auditory FAES was combined with somatosensory stimulation, a large majority (66%) of SIV neurons showed a significant response attenuation. FAES-induced response suppression was specific to SIV, could not be elicited by activating other auditory regions and was blocked by the microiontophoretic application of the GABAergic antagonist bicuculline methiodide. Based on these data, a novel, cross-modal circuit is proposed involving projections from auditory FAES to somatosensory SIV, where local inhibitory interneurons 'reverse the sign' of the cross-modal signals to produce auditory-somatosensory suppression. This form of excitatory-inhibitory multisensory convergence has not been reported before and suggests that the level of interaction between auditory and somatosensory modalities has been substantially underestimated.