Hebbian mechanisms help explain development of multisensory integration in the superior colliculus: a neural network model

Abstract

The superior colliculus (SC) integrates relevant sensory information (visual, auditory, somatosensory) from several cortical and subcortical structures, to program orientation responses to external events. However, this capacity is not present at birth, and it is acquired only through interactions with cross-modal events during maturation. Mathematical models provide a quantitative framework, valuable in helping to clarify the specific neural mechanisms underlying the maturation of the multisensory integration in the SC. We extended a neural network model of the adult SC (Cuppini et al., Front Integr Neurosci 4:1-15, 2010) to describe the development of this phenomenon starting from an immature state, based on known or suspected anatomy and physiology, in which: (1) AES afferents are present but weak, (2) Responses are driven from non-AES afferents, and (3) The visual inputs have a marginal spatial tuning. Sensory experience was modeled by repeatedly presenting modality-specific and cross-modal stimuli. Synapses in the network were modified by simple Hebbian learning rules. As a consequence of this exposure, (1) Receptive fields shrink and come into spatial register, and (2) SC neurons gained the adult characteristic integrative properties: enhancement, depression, and inverse effectiveness. Importantly, the unique architecture of the model guided the development so that integration became dependent on the relationship between the cortical input and the SC. Manipulations of the statistics of the experience during the development changed the integrative profiles of the neurons, and results matched well with the results of physiological studies.

Fig. 1. The general structure of the network in neonatal (fig. 1A) and in mature (fig. 1B – 1C) phase

The four projection areas make excitatory synapses with their target interneurons (arrows). In the neonatal configuration (fig. 1A) only non-AEV and non-FAES input regions are connected with their target SC neurons and their correlated interneurons are effective; on the contrary, projections from AES subregions are not mature and their interneurons haven’t influence on the SC activity. In the adult configuration (fig. 1B) all the four unisensory input areas send excitatory synapses to the SC and the four interneuron populations are effective. These interneurons provide two competitive mechanisms: 1) Ha and Hv provide the bases through which the inhibitory effect of AES is imposed on non-AES inputs; 2) Ia and Iv provide the substrate for a competition between two non-AES inputs in which the stronger one overwhelms the weaker. In panel C, a schematic picture of the network is reported to highlight the more important parameters of the model.

Fig. 2. SC responses and targeting synaptic strengths in the newborn

Responses of a simulated immature SC neuron to different spatial configurations of modality-specific and cross-modal stimuli (a, b). The dark grey circles on the left represent qualitatively the visual RF of a SC neuron, while the light grey circles represent its auditory RF. We used this schematic representation to replicate that adopted by Stein and colleagues (see for example (Wallace and Stein 1997)) to facilitate the comparison between the simulated results and the data present in literature. The neuron is incapable of integrating its two cross-modal inputs and has responses equivalent to those of the stronger of the two. Figures 2.c and 2.d report the strengths of the incoming excitatory synapses that this SC immature neuron receives from the four unisensory input regions; in figures the x-axis represent the position of the pre-synaptic unisensory neurons, while the y-axis reports the synaptic strength of the connections. In this phase, the SC targeting synapses from AES subregions (panels c) are ineffective; on the contrary, the projections from non-AES input areas are diffuse and weak (panels d). Finally, in the neonatal condition, the SC doesn’t present any lateral interaction (fig. 2.e).

Fig. 3. SC targeting synapses in different phases of development

In figures only FAES (left panels) and non-FAES synapses (right panels) are shown. AEV and non-AEV synapses exhibit similar development. In the initial condition (first row), non-AEV synapses are similar but narrower than non-FAES, while AEV synapses are inactive as FAES. X-axis and y-axis represent the position of the pre-synaptic and post-synaptic neuron respectively, while the grayscale denotes the strength of each synapse. Thus, each single row in a panel represents the synapses that target one specific SC neuron. In the immature stage (top row in the figure) the SC receives effective (but weak) synapses only from non-AES areas (specifically, non-FAES for auditory and non-AEV for visual inputs). These inputs provide the sole sensory drive to SC neurons. Connections from AES (i.e., AEV, visual area and FAES auditory area) are not effective, and the very large RFs of SC neurons, in the neonatal condition, reflect the diffuse nature of this projection. In an early stage of the development (after 40.000 steps, second row of panels in the figure), the model presented the first SC multisensory neurons with mature AES-SC synapses (light-grey stripes in the left figure), and pruned non-AES connections (right figure); these synaptic patterns led to a contraction in their RFs. These neurons resulted capable of integrating cross-modal stimuli. In an intermediate stage of the development (after 60.000 steps, third row in the figure), the simulated SC presented an increased number of integrative multisensory neurons, with similar synaptic patterns described above. In a late phase of development, there are just a few non-integrative multisensory neuron in the modeled SC, characterized by widespread projections from non-AES areas (light-grey stripes in the bottom right figure), and non-effective synapses from AES.

Fig. 4. SCN24 responses and targeting synaptic strengths after development

Responses of a simulated immature SC neuron, at the position 24 in the modeled SC area (SCN24), after 100.000 training steps, using the same stimulus configurations as used in Fig. 2(a, b). The neuron is incapable of integrating its two cross-modal inputs and has responses equivalent to those of the stronger of the two. The SC targeting synapses from AES subregions (panels c) are still too weak in this phase, as in the neonatal phase, to elicit an activity in the neuron. In figures the x-axis represents the position of the pre-synaptic unisensory neuron, while the y-axis reports the synaptic strength of the incoming connection. Also projections from non-AES input areas are in a neonatal fashion, diffuse but weak (figures 4.d), and the lateral synapses among SC neurons are still immature (fig. 4.e).

Fig. 5. SCN38 responses and targeting synaptic strengths after development

Responses of a simulated adult SC neuron, in the position 38 of the modeled SC area (SCN38), after 100.000 training steps. The neuron presents cross-modal enhancement (fig. 5.a), but, although it shows modality-specific depression (fig. 5.c), it doesn’t present cross-modal depression (fig. 5.b). In this phase the SC targeting synapses from AES subregions (panels d) are strong enough to drive the activity in the SC neuron and generate the multisensory integration. Projections from non-AES input areas are pruned in an adult-like condition and are stronger with respect to the newborn configuration (fig. 5.e). The overall amount of the lateral synapses of the SC targeting this neurons is still weak and this can be responsible for the lack of the cross-modal depression (fig. 5.f).

Fig. 6. SCN45 responses and targeting synaptic strengths after development

Responses of a simulated adult SC neuron, in the position 45 of the modeled SC area (SCN45), after 100.000 training steps. The neuron presents cross-modal enhancement (fig. 6.a), and depression (fig. 6.b). In this phase the SC targeting synapses from AES subregions (panels c) are strong, and the projections from non-AES input areas are pruned in an adult-like condition (fig. 6.d). The lateral synapses in the SC are effective and generate the cross-modal depression (fig. 6.e).

Fig. 7. Maturation of SCN45 at different training steps

The upper panels show the effect of two cross-modal and within-modal stimuli, at different spatial positions, on the neuron response. In all simulations, an auditory stimulus has been given at the center of the RF, and a second stimulus (either cross-modal or within modal) has been placed at different distances. The x-axis in the upper panels shows the distance between the two stimuli, while the y-axis is the activity of the neuron. Baseline refers to the neuron response to the central auditory stimulus given alone. The bottom panels show the sum of all trained synapses entering the neuron (excitatory descending, excitatory ascending, lateral, inhibitory descending) at different training steps. It is worth noting that descending synapses start to increase abruptly after reaching a given threshold (approximately at step 52000), than rapidly assess at a saturation level. Ascending synapses decrease with training, while lateral synapses become negative, reflecting the predominance of inhibition. These synapses also exhibit the slower dynamics.

Fig. 8. Maturation of SCN38 at different training steps

The meaning of panels is the same as in Figure 7. In this neuron, however, descending synapses develop later (approximately at step 65000) and the lateral synapses are still immature at the end, thus inducing just a poor cross-modal depression in the presence of strong within-modal depression.

Fig. 9. Behavior of a mature multisensory integrative neuron as function of AES cortex

The figures show the activity of a SC neuron (in this case we used the SCN at position 47 in the network) in response to different inputs configurations, with AES active (left panels) and deactivated (right panels). In particular, here we present a neuron which has acquired both integrative capabilities during the development: cross-modal enhancement and multisensory depression. Dynamic Ranges (DRs) (upper figures). In all simulations the activity was assessed by stimulating the model with auditory (dash-dotted line), visual (dashed line) and multisensory (solid line) inputs at various intensities. The stimuli were presented in the center of the RF of the observed SC neuron. Note that with AES active, the simulated SC neuron shows multisensory enhancement in response to a cross-modal stimulation; if the AES is inhibited, the SC shows no multisensory integration, the unisensory responses are reduced by about 50% and the response to two cross-modal stimuli looks like the stronger unisensory one. Integration as a function of the position of two stimuli (lower panels). The figures show the response of the mature SC neuron to paired stimuli in different spatial configurations. Simulations are made by stimulating the model with an auditory (A) stimulus at the center of the RF of the observed SC neuron. The response elicited by this modality-specific stimulus (dashed thin lines) is then compared with those produced by coupling either a second auditory stimulus (dash-dotted lines) or a visual stimulus (solid lines) in different positions. The x axis displays the position of the second stimulus relative to the center of the RF. x = 0° means that both stimuli are at the center of the RF; increasing x means that the position of the second stimulus is increasingly farther from the RF. Results with AES active show: multisensory enhancement in the case of cross-modal stimulation inside the RF irrespective of the position of the two stimuli; no unisensory enhancement in case of a second within-modal stimulus inside the RF; multisensory and unisensory inhibition in the case of two stimuli far in space. In case of AES deactivated, the network shows the loss of multisensory enhancement in case of cross-modal stimulation inside the RF, and a slight inhibition in case of two stimuli of the same or different sensory modality far in space.

Fig. 10. Development of emergent behaviors in the trained SC neurons as a function of the cross-modal input statistics

Panels show the behaviors of the SC neurons in different phases of their maturation, in case of three trainings performed with different cross-modal input statistics. x-axis reports the training phases. y-axis shows the percentage of SC neurons showing a particular emergent behavior. Figure A) presents the sensory abilities of SC neurons in different development phases when the network is trained with just 40% of cross-modal stimuli. The network does not start its maturation since it has been stimulated by 150.000 inputs. Then the AES synapses become effective and the SC neurons begin to present cross-modal integrative capabilities. After about 200.000 training stimuli, immature, multisensory integrative, and unisensory SC neurons coexist in the network. As the training proceeds the multisensory integrative neurons evolve to unisensory, until a mature steady state is reached (at 240.000 stimuli) in which more than the 95% of the SC neurons are modality-specific, and just a few are multisensory. Figure B) presents the behaviors acquired by the SC neurons after a training with 60% of cross-modal inputs: here the network starts its maturation after 100.000 stimuli. As in figure A) in a first phase the network develops multisensory integrative (60%), unisensory (with and without integrative capabilities, 28% and 10% respectively) and still immature (2%) neurons. After 170.000 training stimuli, the network reaches a mature steady state in which there are only unisensory neurons (58% purely unisensory and 42% with integrative capabilities). Finally, Figure C) presents the abilities acquired if the SC is trained with 70% of cross-modal inputs: here the network reaches its maturation final state after about 150.000 stimuli. In this phase 96% of SC neurons are multisensory, while just 4% are unisensory. All of them show integrative capabilities.

Fig. 11. New emergent behaviors in the mature neurons in case of trainings with low cross-modal input statistics

The figures show the dynamic ranges of two SC neurons at the end of a simulated development in which the network has been trained with less than 60% cross-modal inputs. The upper panel reports the responses of a visual neuron, which does not show any integrative capability: a cross-modal stimulation elicits a response no stronger than the activity elicited by a visual stimulus. The lower panel shows the responses of a mature SC neuron which responds only to the auditory modality (visual inputs are almost ineffective), but when a visual stimulus is paired with an auditory one, the neuron presents a clear enhancement of its evoked activity. This neuron can be defined unisensory, but with integrative capabilities acquired along its maturation.

Fig. 12. SC targeting synapses in different phases of development with disparate cross-modal inputs

The figure displays the maturation of synaptic connections between the four unisensory input areas and the neuron in position 80 in the SC area, as the result of a repeated exposure to two cross-modal inputs coincident in time, but not in space. The x-axis represents the position of the pre-synaptic unisensory neurons, while the y-axis reports the synaptic strength of the connections. In particular in this case the visual input is placed in the center of the corresponding RF, whereas the auditory inputs are placed in the RF of unit at position 40 (i.e., about 70° far from the corresponding visual inputs). Panel A) shows the synaptic strength in an early stage of this developmental process. The connections from AES regions are weak and the ascending projections still present an immature arrangement. In this phase the observed SC neuron is maximally responsive for visual and auditory inputs placed in the same position (position 80). Panel B) shows synapses in a late training phase. Finally, panel C) reports the final synaptic configuration. It’s worth noting that the center of the SC auditory RF is spatially shifted (in fact, the RF of the auditory neuron was placed at position 40 in the immature phase, but it is now centered at position 80), reflecting the stimulus position during the training period; as a consequence, the unisensory RFs (i.e. visual and auditory) are no longer overlapped.