Developmental Cortical Plasticity in the Central Auditory System

The brain has a tremendous ability to change as a result of experience. While the brain is plastic throughout life, during early development, the nervous system seems much more sensitive to changes in neural activity or experience. During postnatal critical or sensitive periods, sensory experience can significantly restructure cortical networks, leading to long-term changes in central representations that can affect perception and behavior. This chapter reviews how the parameters of the acoustic environment and inhibitory circuitry can regulate cortical plasticity during early life experience. It highlights newly identified cortical circuit elements that are specifically recruited to engage critical-period plasticity mechanisms.

Pharmacological Manipulation of Critical Period Plasticity

Neuronal networks are refined through an activity-dependent competition during critical periods of early postnatal development. Recent studies have shown that critical period plasticity is influenced by a number of environmental factors, including drugs that are widely used for the treatment of brain disorders. These findings suggest a new paradigm, where pharmacological treatments can be used to open critical period–like plasticity in the adult brain. The plastic networks can then be modified through rehabilitation or psychotherapy to rewire those abnormally wired during development. This kind of combination of pharmacotherapy with physical or psychological rehabilitation may open a new opportunity for a more efficient recovery of a number of neurological and neuropsychiatric disorders.

Environmental Enrichment and Neuronal Plasticity

This chapter reviews the literature on environmental enrichment and specifically discusses its influence on the hippocampus of the brain. In animal models, the term “environmental enrichment” is used to describe a well-defined manipulation in which animals are exposed to a larger and more stimulating environment. This experience has been shown to have a powerful and positive impact on hippocampal cognition and neuroplasticity in animals. In humans, however, the translation of environmental enrichment is less clear. Despite the fact that humans live considerably more enriching lives compared to laboratory animals, studies have shown that training and expertise (such as exercise and spatial exploration) can lead to both functional and structural changes in the human brain. This chapter is a comprehensive review of environmental enrichment, drawing parallels between animal models and humans to present a more complete understanding of environmental enrichment.

Regulation of CNS Plasticity Through the Extracellular Matrix

Contrary to established dogma, the central nervous system (CNS) has a capacity for regeneration and is moderately plastic. Traditionally, such changes have been recognized through development, but more recently, this has been documented in adults through learning and memory or during the advent of trauma and disease. One of the causes of such plasticity has been related to changes in the extracellular matrix (ECM). This complex scaffold of sugars and proteins in the extracellular space alters functionality of the surrounding tissue through moderation of synaptic connections, neurotransmission, ion diffusion, and modification to the cytoskeleton. This chapter discusses the role of the ECM in CNS plasticity in development and the adult. Further, it determines how the ECM affects normal neuronal functioning in critical processes such as memory. Finally, the chapter assesses how the ECM contributes to adverse CNS changes in injury and disease, concentrating on how this matrix may be targeted for therapeutic intervention.

Developmental Consequences of Trauma on Brain Circuits

Traumatic experiences can be challenging at any age, but recent evidence has highlighted the trauma experienced from an attachment figure as particularly detrimental. Fear, or threat, conditioning is a major experimental paradigm that has uncovered the neurobiology of trauma processing. This controlled paradigm has enabled us to understand the changing neurobiology of trauma processing as well as the developmental importance of caregiver presence during trauma. Maternal presence buffers the infant during brief trauma exposure, although repeated trauma in her presence programs the enduring trauma effects on the neurobiology of cognition and emotion. We review the data on innate and learned fear responses across development and describe the interaction between trauma and attachment in early life when threatening cues are processed by the attachment circuitry, rather than fear circuitry, within the brain. This approach can provide insight into age-specific treatments and interventions following infant trauma in the presence of a caregiver.

Cortical Plasticity

The cerebral cortex is a learning engine. The ability to encode information about sensory experience or practiced movements is a universal property of all cortical areas. This capacity, known as cortical plasticity, is seen in experience dependent changes in the functional properties of cortical neurons and in the alteration of cortical circuits. Certain properties are mutable only during a short period in postnatal life, which is known as the critical period, while others retain the ability to change throughout life. The same changes associated with assimilating normal experiences can be implemented for functional recovery following lesions of the central nervous system.

Mediators of Glucocorticoid-Regulated Adaptive Plasticity

The hippocampus has provided a gateway for understanding of how stress, as well as sex hormones, affect cognitive process and has revealed adaptive plasticity in neuronal structure and function throughout the brain and also contributes to damage. This involves direct and indirect epigenomic transcriptional regulation, as well as rapid, non-genomic signaling pathways initiated by membrane-bound glucocorticoid and mineralocorticoid receptors. Downstream of glucocorticoids, multiple mediators—including secreted factors as well as intracellular processes—play critical roles in driving stress-induced remodeling of dendritic arborization and postsynaptic dendritic spines. To understand how these processes act to maintain synaptic homeostasis; prevent permanent, excitotoxic damage; and adaptively regulate learning and decision making, and how we might go about intervening to promote resilience in stress-related neuropsychiatric conditions, new technologies for visualizing and manipulating dendritic spine remodeling and neuronal activity in specific neural circuits are being used to establish causal mechanisms and define new therapeutic strategies.

Oxytocin and Plasticity of Social Behavior

Oxytocin plays well-known roles in modulating social behavior in mammals. Oxytocin function depends on the brain circuitry it modulates, which is determined by the cell-type specific expression of the oxytocin receptor and the network integration of those cells. This review describes emerging evidence for the neural network mechanisms of oxytocin in behavioral plasticity in adults and development. A role for oxytocin in modulating excitatory/inhibitory balance and improving signal:noise processing is an emerging mechanism of function. This emerging literature calls for developmental studies of oxytocin modulation of signal:noise processing in socially naïve circuits. In this review, current oxytocin research findings are placed within the coordinate system of the Uncanny Valley Hypothesis as a model to better understand the role of oxytocin in experience-dependent development and adulthood, to translate research results among diverse mammalian species, and to generate testable predictions for future research.

Organization and Plasticity of Cortical Inhibition

Plasticity of inhibitory synapses keeps inhibition in balance and in register with excitation when changes occur in excitatory synapses. Inhibition has many functions to perform, and there are many kinds of inhibitory neurons to perform various computations and regulate network activity. Different forms of long-term changes in inhibitory synapses have been demonstrated that depend on neural activity. Inhibitory plasticity appears to be partly responsible for the specificity of the inhibitory connections needed to carry out some inhibitory functions. The evolving story of cortical inhibitory plasticity shows that different types of inhibitory interneurons play different roles in a variety of inhibitory functions, that several types of inhibitory plasticity have been attested, and that different forms of plasticity can be expected to have different effects on the organization and specificity of inhibitory connections.