Neuronal activity during development: permissive or instructive?
Introduction
Some aspects of neural circuit development require neural activity to perform with precision. A classic example is the development of ocular dominance columns in visual cortex, which fail to form in the absence of afferent activity arriving from the eyes 1, 2, 3. What remains uncertain is whether the role of neural activity in development is instructive or permissive. In other words, it is not clear whether the pattern of neural activity molds directly the development of the neural connections or whether it is simply the presence of neural activity that enables other developmental cues, such as molecular factors, to guide appropriate neural connections. This review will examine progress over the past year toward distinguishing between an instructive and a permissive role for neural activity in the development of brain circuits. Recent evidence regarding putative cellular and synaptic mechanisms by which neural activity might influence the development of neural circuits will also be discussed.
Section snippets
How can one distinguish between permissive and instructional roles for activity?
The most direct and informative way to distinguish between instructive and permissive roles for neural activity is to change the pattern or information content of the neural activity, while keeping the overall activity constant, and see whether and how this affects the development of neural circuits. The expectation is that different patterns of afferent activity will ‘teach’ or reinforce a different arrangement of connections, perhaps using a competitive mechanism that executes a form of
Spontaneous neural activity during development
Short of a way to substitute for spontaneous activity with artificially induced stimuli, many experimenters have instead explored the effects of simply interfering with spontaneous activity on the development of neural connections. For instance, spontaneous waves of neural activity in the retina, which are present during the development of the visual pathways even before eye opening 8, 9, were recently shown to be necessary for the formation of eye-specific laminae in the ferret lateral
Neural activity in developmental plasticity
The difficulty with directly interfering in the early development of neural connection patterns (because of the fragility of young animals) has led many researchers to alternative experimental approaches. The most common of these is to induce plasticity in partially developed circuits, and then test the role of activity in mediating developmental plasticity. Whether or not the de novo construction of the pattern of neural connections requires instruction from activity is a different question
The amphibian retino-tectal system
In the amphibian visual system, manipulation and observation of the development of the retino-tectal pathway is relatively simple, and many close analogies with the development of mammalian vision can be inferred. For example, the optic tectum normally receives input directly from the contralateral eye only, but can be induced to receive inputs from an ectopic third eye. The doubly innervated tectum then develops eye-preference domains (a.k.a. ocular dominance ‘stripes’) in an
Mechanisms for activity-dependent neural circuit development
An alternative approach to investigating the role of activity in neural circuit development is to interfere with the cellular mechanisms mediating activity-dependent development, without interfering with the activity itself. Changing the ‘instruction’ by modulating the ‘message’ may provide insights into both the mechanism and the message. The NMDA receptor, for the same reasons that it is implicated in learning and memory processes, is a prominent candidate to mediate activity-dependent
Rodent barrel field experiments
The development of some brain structures, particularly early in the establishment of neural pathways, is not directly regulated by neural activity. For example, procedures in which tetrodotoxin (TTX) is applied to essentially the entire brain cavity early in development have resulted in no gross morphological defects in the development of the forebrain and thalamic structures, even though eye-specific laminae in the geniculate nucleus fail to form [11]. These results and those of other
Conclusions
Neural activity is not required for the development of the adult arrangement of all neural connections in the brain. As discussed here, however, there are many instances in which the presence, and perhaps even the pattern, of neural activity is necessary for the formation of precise neural connections. The diversity of apparent effects of neural activity on brain circuit formation may simply define a continuum. This ranges from one extreme, at which neural activity is not at all necessary for
Acknowledgements
I thank John Maunsell and Pamela Petersen-Crair for helpful comments on the manuscript.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
References (52)
- et al.
Blockade of afferent impulse activity disrupts on/off sublamination in the ferret lateral geniculate nucleus
Brain Res Dev Brain Res
(1997) - et al.
Changing patterns of spontaneous bursting activity of on and off retinal ganglion cells during development
Neuron
(1996) Synaptic economics: competition and cooperation in synaptic plasticity
Neuron
(1996)- et al.
Early exploration of the visual cortex
Neuron
(1998) - et al.
Relationship between the ocular dominance and orientation maps in visual cortex of monocularly deprived cats
Neuron
(1997) - et al.
The distribution of afferents representing the right and the left eyes in the cat’s visual cortex
Brain Res
(1977) - et al.
Postnatal blockade of cortical activity by tetrodotoxin does not disrupt the formation of vibrissa-related patterns in the rat’s somatosensory cortex
Brain Res Dev Brain Res
(1992) - et al.
Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice
Cell
(1994) - et al.
NMDA receptor-dependent refinement of somatotopic maps
Neuron
(1997) - et al.
Binocular impulse blockade prevents the formation of ocular dominance columns in cat visual cortex
J Neurosci
(1986)
The role of experience in visual development
Synaptic activity and the construction of cortical circuits
Science
The Organization of Behavior
A physiological mechanism for Hebb’s postulate of learning
Proc Natl Acad Sci USA
Physiological segregation of ocular dominance columns depends on the pattern of afferent electrical activity
Invest Opthalmol Vis Sci
Disruption of orientation tuning in visual cortex by artificially correlated neuronal activity
Nature
Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life
Proc Natl Acad Sci USA
Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina
Science
Competition in retinogeniculate patterning driven by spontaneous activity
Science
Prenatal tetrodotoxin infusion blocks segregation of retinogeniculate afferents
Science
Age-dependent and cell class-specific modulation of retinal ganglion cell bursting activity by GABA
J Neurosci
Experimentally induced retinal projections to the ferret auditory thalamus: development of clustered eye-specific patterns in a novel target
J Neurosci
An adult-like pattern of ocular dominance columns in striate cortex of newborn monkeys prior to visual experience
J Neurosci
The role of visual experience in the development of columns in cat visual cortex
Science
Correlation-based development of ocularly matched orientation and ocular dominance maps: determination of required input activities
J Neurosci
Single-cell responses in striate cortex of kittens deprived of vision in one eye
J Neurophysiol
Cited by (159)
Experience-dependent structural plasticity of pyramidal neurons in the developing sensory cortices
2023, Current Opinion in NeurobiologyThe Inductive Brain in Development and Evolution
2021, The Inductive Brain in Development and EvolutionActivity regulates brain development in the fly
2020, Current Opinion in Genetics and DevelopmentCitation Excerpt :Whether it is the rhythmic, coordinated contractions of the locomotor system along the spinal column [2] or the sweeps of excitation that spread across the mammalian retina [3], these highly structured regimes of activity seem too information-rich not to be playing an important role in wiring the CNS. The question of whether this order in the activity does guide neuronal development has been formalized in the classic framework of instructive versus permissive mechanisms [4]. The proposed test for an instructive role is to ask whether development is disrupted when the activity is experimentally altered to change the patterns while preserving overall levels [4].
Retinal waves and their role in visual system development
2020, Synapse Development and Maturation: Comprehensive Developmental NeuroscienceImaging the Emergence of Behavior
2019, CellCitation Excerpt :The successful formation of functional circuits during nervous system development is crucial for the survival of animals. Development establishes the gross anatomy of circuits, which is often subsequently refined in an activity- and experience-dependent manner (Crair, 1999). Interestingly, developing circuits exhibit intrinsic, i.e., spontaneous and stereotypically patterned, activity, which was observed in many brain regions such as the spinal cord (SC), the retina, and the cerebellum (Blankenship and Feller, 2010).