Experience-dependent plasticity, a fundamental process in the brain’s ability to adapt to changing environments, has long been attributed to the cortex. However, recent studies have revealed that plasticity is not confined to cortical regions but also extends to the dorsal lateral geniculate nucleus (dLGN) of the thalamus in adult organisms.
It explores how plasticity in the adult dLGN is regulated and how this thalamic region interacts with the primary visual cortex (V1) during ocular dominance (OD) plasticity in mice.
Experience-dependent plasticity is a pivotal mechanism by which the brain adapts to the sensory input it receives throughout life. Traditionally, this process has been closely associated with cortical regions, particularly the primary sensory cortex. However, groundbreaking research has begun to unveil a more complex picture of plasticity, implicating subcortical structures such as the dorsal lateral geniculate nucleus (dLGN) of the thalamus.
The concept of ocular dominance (OD) plasticity serves as an excellent model for studying experience-dependent plasticity in the visual system. OD refers to the phenomenon where neurons in the visual system preferentially respond to visual stimuli presented to one eye over the other. This property is a result of sensory experience and can be modulated by various factors, including monocular deprivation (MD).
Ocular Dominance Plasticity: A Window into Experience-Dependent Plasticity
Historically, OD plasticity was primarily studied during development’s critical period, during which substantial changes in the brain’s wiring and function can occur. However, recent studies have demonstrated that OD plasticity can also be induced in young adult mice with a more extended period of MD. Although the plasticity during adulthood requires a more prolonged deprivation period and is less pronounced than during the critical period, it has opened a new avenue for exploring the mechanisms underlying adult plasticity.
Thalamus and Plasticity: A Surprising Connection
The thalamus, long considered a relay station transmitting sensory information to the cortex, was traditionally believed to play a passive role in plasticity. Nevertheless, research conducted in recent years has challenged this notion. A pivotal study by Sommeijer et al. (2017) found that extensive OD plasticity can be induced in the dLGN during the critical period and that this process critically depends on synaptic inhibition in the thalamus.
Specifically, the research utilized mice in which thalamic synaptic inhibition was inactivated by selectively deleting the gene encoding the GABA receptor alpha1 subunit (Gabra1) in the dorsal thalamus. These mice, referred to as “KO mice,” displayed a significant reduction in OD plasticity in both dLGN and V1. Intriguingly, this suggested that during the critical period, thalamic plasticity plays a role in shaping plasticity in V1. This finding opened up a fascinating avenue for further investigation.
The Dynamic Interplay between dLGN and V1 in Adult Plasticity
Building upon their earlier work, the researchers in this study sought to unravel the intricate interactions between dLGN and V1 during OD plasticity in adult mice. One of the central questions addressed was whether thalamic plasticity in the dLGN could still influence plasticity in the cortex during adulthood.
Surprisingly, their findings indicated that in adult mice lacking thalamic synaptic inhibition, OD plasticity was entirely absent in both the dLGN and V1. This observation highlighted the critical role of thalamic inhibition in governing experience-dependent plasticity in the adult visual system.
To further dissect the interplay between these two regions, the researchers also explored whether silencing V1 in adult wild-type (WT) mice had any effect on OD plasticity in dLGN. Strikingly, they found that silencing V1 did not disrupt the OD shift in dLGN. This result suggested that the dLGN’s plasticity did not rely on feedback from V1 in adulthood.
However, when the study turned its attention to the critical period of development, a different picture emerged. During this developmental phase, the OD shift in dLGN was found to partially depend on activity in V1. This finding underscored the dynamic nature of thalamocortical interactions during OD plasticity, revealing that these interactions change as the brain matures.
In this study, we have delved into the fascinating world of ocular dominance (OD) plasticity in the dorsal lateral geniculate nucleus (dLGN) and its interplay with the primary visual cortex (V1) in adult mice. Our findings shed light on the critical role of thalamic synaptic inhibition in governing experience-dependent plasticity, challenging the conventional notion that plasticity is solely a cortical process. This discussion chapter will explore the implications and complexities of our results in the broader context of neurobiology and its potential applications in understanding brain disorders and learning mechanisms.
Thalamic Plasticity and Ocular Dominance Shift
Our study unequivocally demonstrates that OD plasticity in the dLGN of adult mice is markedly reduced when thalamic synaptic inhibition is lacking. In these conditions, not only is OD plasticity in the dLGN hampered, but a surprising absence of OD plasticity is also observed in V1. This intriguing observation suggests a close link between thalamic and cortical plasticity during adulthood, challenging the conventional view of cortical dominance in plasticity processes.
Absence of V1 Feedback in Adult Mice
Our results further indicate that, contrary to expectations, feedback from V1 does not appear to affect the thalamic OD shift in adult mice. This finding diverges from the situation during the critical period, where the OD shift in the dLGN partly depends on V1 activity. The absence of V1 feedback in adulthood suggests that the thalamus can independently undergo plasticity, highlighting the dynamic nature of thalamocortical interactions that evolve with age.
Differential OD Plasticity During the Critical Period
During the critical period, our study reveals that the OD shift in the dLGN is partially inherited from V1, emphasizing the continuous interplay between these two regions during development. This suggests that V1 feedback plays a more substantial role in shaping thalamic plasticity during early stages of life, where the brain is highly adaptable and responsive to sensory experiences.
The Role of Retinogeniculate Synapses
Our investigation indicates that the primary substrate of OD plasticity in adult dLGN is the retinogeniculate synapse. This finding is consistent with previous studies suggesting that silent synapses, dominated by NMDA receptors, are involved in OD plasticity in dLGN. The unsilencing and strengthening of these synapses may contribute significantly to the OD shift observed in adult mice, highlighting a potential target for future research.
Contradictory Findings and Methodological Considerations
In contrast to our results and those of other studies, a recent investigation did not observe an OD shift in the dLGN of adult mice after a period of monocular deprivation. We propose that this apparent discrepancy may be attributed to methodological differences, particularly in the selection of neurons for analysis. Excluding monocular, contralateral-eye selective neurons from the analysis could underestimate the measured OD shift, potentially accounting for the differences observed in different studies.
Understanding the Developmental Aspect
Our study also raises questions about the developmental aspect of thalamic plasticity. While we did not find evidence for halted thalamic development in adult KO mice, it remains a possibility that adult KO mice exhibit a pre-critical period-like state in dLGN plasticity. However, the lack of differences in receptive field sizes and other developmental markers suggests that thalamic development remains intact, and the primary distinction between WT and KO mice is the absence of synaptic inhibition.
Impact on Cortical Plasticity
The critical question arises: How does the inactivation of synaptic inhibition and OD plasticity in dLGN affect the OD shift in V1? Our data suggest that OD plasticity in V1 is not deficient due to halted development in a pre-critical period-like state. The observed plasticity deficit in V1 during the critical period appears to be limited to the late phase of the OD shift, which requires long-term monocular deprivation.
The most straightforward explanation for this cortical plasticity deficit is that changes in dLGN relay cell responses to inputs from both eyes contribute to the OD shift in V1. Additionally, the strengthening of responses to the non-deprived eye in dLGN neurons may provide their axons with a competitive advantage during OD plasticity in V1, further enhancing the OD shift in the cortex. Lastly, the alteration in spike-dependent plasticity due to the attenuated nature of dLGN responses in KO mice may also play a role in affecting cortical plasticity.
Methodological Considerations and the Role of Feedback
Our findings also highlight the complexity of feedback from V1 to dLGN. While studies involving optogenetic stimulation of layer 6 neurons have shown that feedback from V1 can suppress dLGN responses, our research indicates that the average strength of dLGN responses is not significantly reduced when V1 is silenced. This discrepancy may be attributed to the nature of feedback, with optogenetic stimulation predominantly recruiting inhibitory feedback, while visual stimulation provides a more balanced or limited feedback. The precise mechanisms underlying this discrepancy warrant further investigation.
Implications for Understanding Brain Disorders
Our study has broader implications beyond understanding the intricacies of OD plasticity. It underscores the importance of thalamic involvement in brain disorders, including amblyopia and learning disabilities. Thalamic plasticity’s potential role in these conditions should not be underestimated, as our results indicate that it may contribute significantly to their pathophysiology.
Additionally, our findings may offer insights into disorders involving dysfunctional thalamocortical circuits, such as attention deficit disorder and schizophrenia. Understanding how thalamic plasticity influences these conditions could open new avenues for therapeutic interventions.
The questions raised by our research pave the way for future investigations into the mechanisms underlying thalamic plasticity and its influence on cortical plasticity. Further experiments focusing on changes in thalamic responses, the role of unsilenced synapses, and the temporal dynamics of visual responses are needed to gain a more comprehensive understanding of thalamocortical interactions.
Moreover, studies in species with more strictly separated layers in the dLGN, such as cats or primates, may provide additional insights into the generality of adult thalamic OD plasticity. The potential for thalamic plasticity to contribute to amblyopia and other visual disorders in humans remains a promising avenue for future research.
In conclusion, this study sheds new light on the intricate world of experience-dependent plasticity in the adult visual system, challenging conventional views that limited plasticity to cortical processes. The findings indicate that the dorsal lateral geniculate nucleus (dLGN) of the thalamus plays a pivotal role in governing plasticity in both the thalamus itself and the primary visual cortex (V1) during OD plasticity.
The research demonstrates that thalamic synaptic inhibition is a crucial regulator of plasticity in the dLGN and V1 during the critical period and in adulthood. The absence of OD plasticity in adult mice lacking thalamic synaptic inhibition highlights the significance of this inhibitory control. Additionally, the study’s differential findings for the critical period and adulthood reveal that thalamocortical interactions evolve with age, suggesting that the thalamus might be a previously underestimated source of plasticity in adult learning processes.
These insights not only expand our understanding of the neural mechanisms underlying experience-dependent plasticity but also underscore the complexity of interactions between different brain regions in adapting to sensory experiences throughout life. Future research may further elucidate the molecular and cellular processes that underlie these phenomena, potentially paving the way for novel approaches in enhancing adult learning and rehabilitation.
reference link : https://elifesciences.org/reviewed-preprints/88124v2