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Elevated Synaptic Plasticity as a Potential Driver of Enhanced Cognition and Perseveration in Autism

Submitted:

18 April 2026

Posted:

20 April 2026

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Abstract
Autism is characterized by differences in cognition, behavior, and information processing that are often linked to alterations in neural circuit function. Synaptic plasticity—particularly long-term potentiation (LTP) and long-term depression (LTD)—plays a central role in learning, memory, and the adaptive updating of neural circuits. Here, we propose a mechanistic model in which a shift toward excessive synaptic strengthening, coupled with disrupted synaptic weakening, may contribute to core features associated with autism. Heightened plasticity in hippocampal–cortical, striatal, and cerebellar circuits may bias neural systems toward the persistent reactivation of previously formed activity patterns, limiting the flexible encoding of new information. Such dynamics could manifest as reduced cognitive flexibility, repetitive behaviors, and differences in language and social function. At the same time, similar mechanisms may, in certain contexts, support enhanced cognitive abilities, including exceptional memory and pattern recognition, suggesting that maladaptive persistence and enhanced function may arise from shared underlying processes. This perspective integrates findings from electrophysiological, genetic, and behavioral studies and proposes that autism may involve a shift in synaptic learning rules toward disproportionate stabilization of neural activity. It generates testable predictions regarding circuit-level plasticity and highlights potential strategies for modulating these processes to restore a balance between stability and flexibility in neural systems.
Keywords: 
autism
;  
synaptic plasticity
;  
cognitive flexibility
;  
neural circuits
;  
hippocampal–cortical networks
;  
long-term potentiation
;  
long-term depression
;  
neural encoding
;  
perseveration
;  
excitatory–inhibitory balance
Subject: 
Biology and Life Sciences  -   Neuroscience and Neurology

A Potential Role for Altered Synaptic Plasticity in Autism

When we learn something new or experience novel places, distributed populations of neurons within the brain adjust the strength of their connections, subtly reshaping the flow of information through neural circuits [1]. This process—known as synaptic plasticity—is widely considered a fundamental mechanism underlying learning, memory formation, and the adaptive tuning of behavior across distributed neural systems. Such plasticity within hippocampal–cortical networks supports the acquisition of social [2] and linguistic abilities [3,4], as well as the flexible updating of learned information [5], while synaptic changes within motor-related circuits—including the cortex, cerebellum, and basal ganglia—underlies coordinated and sequential motor behaviors [6,7].
Here, we consider the possibility that alterations in these mechanisms—particularly a shift toward excessive synaptic strengthening and stabilization—may contribute to core features of autism. Such changes may manifest as reduced cognitive flexibility, repetitive behaviors, and differences in language processing and social interaction, potentially reflecting an imbalance between the encoding of new information and the persistence of previously formed neural patterns. These alterations may be especially pronounced during critical periods of development, when neural circuits exhibit heightened sensitivity to experience-dependent remodeling and early activity patterns can exert lasting influence on circuit organization [8].
Consistent with this framework, a growing body of evidence suggests that synaptic transmission and plasticity are altered in autism [9,10,11,12,13,14,15,16,17,18,19,20,21], alongside abnormalities in critical period regulation [13,20]. Long-term potentiation (LTP), a major form of plasticity, is widely considered a cellular correlate of learning and memory. If LTP were excessively active during key developmental periods—affecting circuits underlying memory, language, social interaction, and motor learning—neural systems may become biased toward sustained strengthening rather than maintaining a balance between potentiation and weakening. In this context, neural engrams—ensembles of neurons representing specific memories—may be reactivated too frequently, making it difficult to update or override previously established activity patterns.
If heightened plasticity occurs within hippocampal and downstream cortical circuits, it could impair the encoding of new information while biasing neural activity toward previously established states. In this way, the past may begin to intrude upon the present, contributing to repetitive behaviors and challenges in communication and social interaction. Similar mechanisms within motor circuits, such as the basal ganglia and cerebellum, could drive repetitive and rhythmic behaviors.
Multiple electrophysiological studies in animal models associated with autism-linked genes demonstrate altered synaptic plasticity, including enhanced LTP in hippocampal [22,23,24,25,26] and cortical circuits [27], as well as excessive synaptic strengthening in cerebellar networks [28]. Human neurophysiology studies using non-invasive LTP-like paradigms have also reported altered plasticity responses in individuals on the autism spectrum [29].
While excessive strengthening may contribute to persistence, alterations in long-term depression (LTD)—a process that weakens synaptic transmission—may also play a role. Long-term depression (LTD) is critical for updating learned behaviors and enabling flexible adaptation [30]. Disruptions in LTD—particularly within cortico-striatal circuits—may limit the ability to suppress or extinguish previously reinforced patterns [31]. In mouse models of autism, impairments in endocannabinoid (eCB)-mediated LTD at cortico-striatal synapses have been reported [32,33,34] suggesting a reduced capacity for synaptic weakening. Together, these findings suggest that autism may not arise solely from increased synaptic strengthening, but from a coordinated alteration in the balance of plasticity processes—shifting learning rules toward disproportionate potentiation and reduced capacity for synaptic weakening. Altered plasticity across hippocampal, cortical, basal ganglia, and cerebellar circuits may therefore reinforce previously formed memories and behaviors, limiting their modification or integration into more complex frameworks.
Although these changes manifest as impairments in many individuals, rare cases suggest that similar mechanisms may also support enhanced cognition. Autistic savants, for example, can rapidly compute, recall, or reproduce complex information—such as calculating calendar dates, recalling detailed autobiographical events, or reproducing musical compositions after a single exposure. In some cases, these abilities are striking: an individual may determine the day of the week for a distant historical date—such as July 21, 356 B.C. (Sunday)—within seconds.
Within hippocampal–cortical networks, overactive synaptic plasticity may contribute to unusually strong autobiographical memory, while sustained activity in frontoparietal cortical networks may enable extended sequences of computation or performance. Indeed, some individuals can recall events from nearly every day of their lives; within this framework, such abilities may be associated with autism or autism-related traits, as has been reported in certain cases [35]. This observation raises the possibility that enhanced synaptic strengthening—particularly within hippocampal–cortical networks—may support the formation and long-term retention of richly detailed autobiographical memories.
More broadly, overactive plasticity may enable extended patterns of neural activity that unfold over seconds to minutes—patterns that would typically degrade more rapidly in most individuals. In such cases, cognition may remain continuously linked across time—extending from the first note to the last while playing a piano piece after hearing it just once; through the uninterrupted execution of complex mathematical calculations; or from the present moment back to a distant historical date, such as Alexander the Great’s birth, traced accurately across more than two millennia.
Spanning rhythm, memory, and complex computation—these capacities may reflect a shared shift in synaptic learning dynamics that gives rise to the defining features of autism, suggesting that enhanced abilities and maladaptive persistence are distinct outcomes expressed across different brain regions or more selectively constrained in individuals with exceptional abilities.
At a more everyday level, this same shift may manifest in familiar behaviors observed across the autism spectrum.
Consider a nine-year-old child with autism who repeatedly says the unique name “Solara” out of context throughout the day during his third session at a behavioral center. Solara is the name of a behavioral technician he met two weeks earlier during his first visit, but the technician is not present during this session. Following that initial encounter, the child likely formed neural engrams representing both the novel environment and the associated person and name “Solara,” through activity-dependent plasticity within hippocampal–cortical circuits.
What if, instead of these memories being encoded and flexibly accessed when appropriate, they become over-consolidated? The neural activity pattern representing “Solara” may be replayed excessively—during wakefulness and potentially during sharp wave ripple–associated events during sleep—further strengthening the underlying synaptic connections. As a result, the child’s brain may become biased toward recalling and expressing this memory, even when it is no longer contextually relevant.
A similar phenomenon is observed when the child repeatedly says “Ding, time’s up!” in a sensory room. During his first visit, he was timed for a break in the sensory room; a timer sounded (“ding!”) just before his supervisor said something to the effect of “time’s up” and ushered him out. Here, specific elements—including auditory cues and associated motor outputs—appear to have become tightly linked through synaptic strengthening. These co-activated patterns may be reinstated as a unit, making the behavior difficult to suppress or update. Once in the sensory room, the child cannot help but say “Ding, time’s up,” just as he cannot be in the broader environment of the center without repeatedly saying “Solara,” whose neural pattern has become strongly associated with that spatial and social context.
During his third session, the child did not use the name of his new behavioral technician or even his familiar behavior analyst—only “Solara.” In this way, his behavior appears dominated by the repeated reactivation of earlier-formed neural patterns, rather than real-time integration of new information. This could be likened to individuals with autism living in the echoes of previous (and often novel) experiences, with hippocampal–cortical circuits biased toward replay rather than encoding new input. This interpretation is consistent with findings of enhanced synaptic plasticity in hippocampal CA1 circuits—an area critically involved in memory encoding and recall—in animal models of autism19.
Dopaminergic signaling, which is engaged by novel stimuli [36,37] and facilitates long-term synaptic plasticity within hippocampal circuits [38,39,40], may further bias the consolidation of early experiences. Dysregulation of dopamine has been implicated in autism [41] and in perseverative behavior [42,43], suggesting that alterations in neuromodulatory signaling may reinforce the stabilization and repeated reactivation of prior activity. Within this framework, excessive stabilization of early activity patterns, especially those linked to novel experiences, may limit the flexible updating of network states required for ongoing learning and adaptation.
Numerous studies support the involvement of altered plasticity and critical period dysfunction in autism. In a mouse model of autism/Angelman syndrome, for instance, deficits in synaptic plasticity associated with critical period remodeling of cortical visual circuits have been observed9. In vitro analyses further revealed that cortical synapses remained immature and were unable to effectively incorporate new sensory information. These findings suggest that neural circuits may become less capable of integrating new experiences over time when earlier patterns are excessively stabilized—functionally biasing the system toward previously established activity patterns. Structurally, neurons in autism exhibit increased dendritic spine density [10,11], which may reflect prolonged synaptic connectivity and contribute to persistent encoding. Consistent with this, abnormalities in plasticity have been observed across multiple genetic models, including Fragile X syndrome [12,13], Rett syndrome [14,15], and Tuberous sclerosis [16,17]. Enhanced plasticity has also been reported in models such as Shank2 knockout mice [18] and Lrfn2 knockout mice [19], the latter of which show increased memory formation, supporting a shift toward strengthened and enduring neural encoding.
At the behavioral level, these alterations may manifest as a tendency to become “stuck” in patterns of thought or action. Earlier neural patterns—associated with language, social interaction, and motor behavior—may become excessively reinforced, limiting the ability of circuits to evolve beyond these initial states. In contrast, typical development involves flexible templates that are progressively reshaped by experience; when this flexibility is reduced, development may become constrained, with neural systems repeatedly reinstating earlier patterns rather than building upon them.

Potential Interventions

When considering these features, it becomes important to distinguish between mechanisms that contribute to maladaptive persistence and those that may support enhanced cognitive function. Therapeutic strategies may therefore aim not to eliminate these processes, but to regulate them—reducing excessive persistence while preserving adaptive capacity.
Given that synaptic plasticity is governed by converging signaling pathways, approaches capable of modulating multiple targets simultaneously may be particularly relevant. Cannabis-derived compounds, including cannabinoids and terpenes, interact with a range of molecular systems—including CB1 receptors [44,45], GPR55 [46,47], TRP channels [48,49,50], 5-HT1A receptors [51], GABAergic receptors [52,53], NMDA receptors [54,55], and several voltage-gated ion channels [56,57,58,59,60]—that regulate synaptic transmission and excitability. Through coordinated modulation of these pathways, such approaches may help refine synaptic strengthening and weakening, as well as restore excitatory–inhibitory balance—processes thought to be altered in autism [61]—thereby promoting the cognitive flexibility necessary for learning. Consistent with this, mechanistic frameworks propose that multi-compound cannabinoid–terpene interactions may influence circuit-level excitatory–inhibitory balance in autism [62].
More broadly, identifying circuit-specific abnormalities in plasticity may enable targeted interventions. Functional imaging, behavioral phenotyping, and genetic profiling may help localize regions exhibiting aberrant dynamics. Emerging approaches—including optogenetic [63], chemogenetic [64,65], and cell-specific pharmacological tools [66]—illustrate how circuit-level understanding may inform precision therapies aimed at restoring balanced plasticity. Modulating these systems could help restore the balance between stability and flexibility necessary for adaptive learning.

Conclusions

In the distant future, traits associated with autism—such as enhanced memory, pattern recognition, and rapid information processing—may become more widely distributed, while maladaptive features are mitigated through refinement of existing biological systems. Such changes would not require new mechanisms, but rather the tuning of processes governing synaptic plasticity, circuit specificity, and developmental timing.
Autism can be a profoundly challenging condition, yet within it may lie the cellular and molecular substrates of heightened cognitive processing. Understanding these mechanisms may not only inform therapeutic strategies but also deepen our understanding of the range and potential of human neural function.

Acknowledgments

The author thanks Dr. Michael Tadross for insightful discussions and critical feedback on the manuscript.

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