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A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test.

Herreros I, Giovannucci A, Taub AH, Hogri R, Magal A, Bamford S, Prueckl R, Verschure PF - Front Bioeng Biotechnol (2014)

Bottom Line: As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response.The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region.These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

View Article: PubMed Central - PubMed

Affiliation: Synthetic Perceptive, Emotive and Cognitive Systems group (SPECS), Universitat Pompeu Fabra , Barcelona , Spain.

ABSTRACT
Emulating the input-output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model's inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

No MeSH data available.


Related in: MedlinePlus

Biological microcircuit and synthetic counterpart. Recording (PN and IO) and stimulation sites are shown. After amplification and filtering of the signals recorded in the afferent structures, discrete events retrieved from multi unit activity are isolated by the event detection stages of the system, such that they are fed to their counterparts in the synthetic cerebellum (PN and IO). In the intact circuit, the repeated coincidence of CS and US signals within the cerebellar cortex induces plasticity causing the cerebellum to respond to the CS with a CR. In our model, once such a CR is acquired, it is relayed via the synthetic DN to the facial nucleus (FN) of the rat as an electrical stimulation that causes the animal to trigger the behavioral CR, i.e., the eye-blink. In addition, within the model, the CR triggered by the DN inhibits the IO, preventing a US-derived signal from reaching the cerebellum once a protective action has already been issued. Since anesthesia prevents acquisition in the rodent’s cerebellum, behavioral CRs expressed in the set up studied here are controlled by the synthetic circuit.
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Figure 1: Biological microcircuit and synthetic counterpart. Recording (PN and IO) and stimulation sites are shown. After amplification and filtering of the signals recorded in the afferent structures, discrete events retrieved from multi unit activity are isolated by the event detection stages of the system, such that they are fed to their counterparts in the synthetic cerebellum (PN and IO). In the intact circuit, the repeated coincidence of CS and US signals within the cerebellar cortex induces plasticity causing the cerebellum to respond to the CS with a CR. In our model, once such a CR is acquired, it is relayed via the synthetic DN to the facial nucleus (FN) of the rat as an electrical stimulation that causes the animal to trigger the behavioral CR, i.e., the eye-blink. In addition, within the model, the CR triggered by the DN inhibits the IO, preventing a US-derived signal from reaching the cerebellum once a protective action has already been issued. Since anesthesia prevents acquisition in the rodent’s cerebellum, behavioral CRs expressed in the set up studied here are controlled by the synthetic circuit.

Mentions: The cerebellum is critical for the acquisition of CRs in eye-blink conditioning (Hesslow and Yeo, 2002; Christian and Thompson, 2003). The CS signal reaches the cerebellum through the mossy fibers originating in the Pontine Nuclei (PN), while the US signal is projected through the climbing fibers originating in the Inferior Olive (IO). These two projections converge onto the cerebellar Purkinje cells that control through dis-inhibition of the deep nuclear cells. Deep nuclear neurons synapse with the motor neurons responsible for the production of CRs. Purkinje cells, the sole output of the cerebellar cortex, thus indirectly control the motor neurons with an inverse relationship, they drive CRs by learning to timely reduce their activity in presence of the CS (Jirenhed et al., 2007). These areas of the cerebellar cortex, cerebellar nuclei, and IO regulating the acquisition of conditioned eye-blinks constitute one of the many cerebellar microcircuits, which are considered the elementary and parallel computational units that form the cerebellum (see Figure 1).


A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test.

Herreros I, Giovannucci A, Taub AH, Hogri R, Magal A, Bamford S, Prueckl R, Verschure PF - Front Bioeng Biotechnol (2014)

Biological microcircuit and synthetic counterpart. Recording (PN and IO) and stimulation sites are shown. After amplification and filtering of the signals recorded in the afferent structures, discrete events retrieved from multi unit activity are isolated by the event detection stages of the system, such that they are fed to their counterparts in the synthetic cerebellum (PN and IO). In the intact circuit, the repeated coincidence of CS and US signals within the cerebellar cortex induces plasticity causing the cerebellum to respond to the CS with a CR. In our model, once such a CR is acquired, it is relayed via the synthetic DN to the facial nucleus (FN) of the rat as an electrical stimulation that causes the animal to trigger the behavioral CR, i.e., the eye-blink. In addition, within the model, the CR triggered by the DN inhibits the IO, preventing a US-derived signal from reaching the cerebellum once a protective action has already been issued. Since anesthesia prevents acquisition in the rodent’s cerebellum, behavioral CRs expressed in the set up studied here are controlled by the synthetic circuit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126458&req=5

Figure 1: Biological microcircuit and synthetic counterpart. Recording (PN and IO) and stimulation sites are shown. After amplification and filtering of the signals recorded in the afferent structures, discrete events retrieved from multi unit activity are isolated by the event detection stages of the system, such that they are fed to their counterparts in the synthetic cerebellum (PN and IO). In the intact circuit, the repeated coincidence of CS and US signals within the cerebellar cortex induces plasticity causing the cerebellum to respond to the CS with a CR. In our model, once such a CR is acquired, it is relayed via the synthetic DN to the facial nucleus (FN) of the rat as an electrical stimulation that causes the animal to trigger the behavioral CR, i.e., the eye-blink. In addition, within the model, the CR triggered by the DN inhibits the IO, preventing a US-derived signal from reaching the cerebellum once a protective action has already been issued. Since anesthesia prevents acquisition in the rodent’s cerebellum, behavioral CRs expressed in the set up studied here are controlled by the synthetic circuit.
Mentions: The cerebellum is critical for the acquisition of CRs in eye-blink conditioning (Hesslow and Yeo, 2002; Christian and Thompson, 2003). The CS signal reaches the cerebellum through the mossy fibers originating in the Pontine Nuclei (PN), while the US signal is projected through the climbing fibers originating in the Inferior Olive (IO). These two projections converge onto the cerebellar Purkinje cells that control through dis-inhibition of the deep nuclear cells. Deep nuclear neurons synapse with the motor neurons responsible for the production of CRs. Purkinje cells, the sole output of the cerebellar cortex, thus indirectly control the motor neurons with an inverse relationship, they drive CRs by learning to timely reduce their activity in presence of the CS (Jirenhed et al., 2007). These areas of the cerebellar cortex, cerebellar nuclei, and IO regulating the acquisition of conditioned eye-blinks constitute one of the many cerebellar microcircuits, which are considered the elementary and parallel computational units that form the cerebellum (see Figure 1).

Bottom Line: As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response.The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region.These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

View Article: PubMed Central - PubMed

Affiliation: Synthetic Perceptive, Emotive and Cognitive Systems group (SPECS), Universitat Pompeu Fabra , Barcelona , Spain.

ABSTRACT
Emulating the input-output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model's inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

No MeSH data available.


Related in: MedlinePlus