News & Media
A tad better understanding of how our brains are wired
The human brain is the most complex machine that you will ever encounter. Weighing in at just over 1kg, it is a data processing marvel, capable of simultaneously reconstructing an annotated, three-dimensional mental representation of the room you are standing in, coordinating the fine interactions of your more than 600 skeletal muscles, and appreciating the complex tannins of a robust cabernet sauvignon, all effortlessly and in parallel. On the other hand, the brain of a stage 48 Xenopus tadpole, like the ones we study in my lab, weighs a mere 1mg (roughly one one-millionth the mass of a human brain!). To be fair, a stage 48 tadpole has a proportionately less intellectually demanding lifestyle, spending much of its day swimming in a circle “hoping” a morsel of edible substance will enter its mouth in the process -- moreover, they actually prefer to drink water! So what exactly can this very simple tadpole brain teach us about how our brains carry out complex perceptual tasks?
That internal 3D representation of the room you’re sitting in is obviously the result of your having looked around and determined the relative spatial relationships between the walls, furniture and other objects that surround you. These perceptions in turn have driven modifications of synaptic connections in your brain that allowed you to build an internal picture of the room. But what about more basic processing tasks? As you reach for the glass you see your hand move to your right. Is it possible that something as fundamental as the perception of directional movement of objects also needs to be learned by experience? Experiments on ferrets in David Fitzpatrick’s lab at Duke University suggest that indeed this may be the case. During the first month of life neurons in the ferret visual cortex normally acquire response selectivity to visual stimuli moving in specific directions – each neuron will fire best to an object moving in a certain direction, and all possible directions are represented by the full ensemble of cortical neurons. If animals are reared in complete darkness during this early critical period, however, these neurons never learn to discriminate direction and the ability fails to emerge later in life despite subsequent normal visual experience. Moreover, if very young animals, prior to the time when direction selective neurons are normally observed, are presented with repetitive directional visual stimulation in just one part of their visual field, the cortical neurons representing that part of visual space develop precocious direction selectivity. So the ability to visually perceive directional movement appears to depend on appropriate early sensory experience that helps pattern key synaptic connections.
It turns out that lowly Xenopus tadpoles are in fact quite similar to mammals in this regard. Repeated visual training with a directional stimulus also causes neurons in the primary visual area of the tadpole’s brain, the optic tectum, to shift their direction preference to favor the trained direction. Neil Schwartz, a graduate student in my lab recently discovered that not all tadpoles are equally up to this task. Tadpoles that several hours prior had received an intensive visual conditioning stimulation, shown previously to enhance dendritic growth rates and gene transcription in tectal neurons, exhibited elevated levels of synaptic plasticity resulting in an improved ability to shift the direction preference of their tectal cells. This enhanced plasticity turns out to result in large part from activity-dependent production of the neurotrophic factor BDNF driven by that earlier conditioning stimulation.
The take-home message is that prior sensory experience has multiple effects on the refinement of circuitry mediating perception. In the case of directionality, it can provide instructive cues to train the immature circuit to distinguish between different directions. But more generally, it also activates a permissive modification of the transcriptional status of the cells in the circuit in a way that alters how they will be modified by ongoing sensory stimuli – in a sense it sets the gain control for circuit changes. Importantly, for human development, this means that as we search for genetic factors responsible for developmental disorders of neural connectivity, as schizophrenia and autism are thought to be, our search should extend beyond factors that directly alter synaptic connectivity and include transcriptional regulators and signaling modulators that may have a much broader but indirect role in plasticity.
