How are hereditary neural circuits created in the brain during early development?

Question

Whilst our experiences shape the specifics of our brains throughout life, we know that there are a lot of shared properties between us. We all share the same basic layout as, for example, the V1 cortex is always in the same place. Thus it is evident that whilst some of the neural development is experience-dependent, some of it is hereditary/genetic or "hard wired".

It would seem to me that the extent to which the brain is "hard wired" depends on the species. Humans seem to have a lot more room for specialisation in life, whereas some animals don't exhibit much individuality, tending to follow very regular behavioural patterns that have no doubt evolved over time, subject to natural selection.

I have read up to some degree on how experience-dependent development works, but have been largely unable to find any detailed research into how experience-independent development works. That is, how does DNA encode these "hard wired" neural circuits?

Furthermore, the human brain contains some 100 billion neurons. If I assume that maybe 1% of them are "hard wired" into circuits from birth, that's still a billion neurons, each with several connections to other neurons that need to be somehow coded into a DNA sequence which only amounts to a couple of gigabytes worth of data. So how is the complex structure of these "hard wired" (experience-independent) neural circuits encoded in such a limited amount of DNA? How much of the brain is actually hard wired in this way and how much is open to experience-based development? Am I right in associating this process with the phenomenon of "instinct", that is, "hard coded" behavioural patterns in animals which appear to be hereditary?

Is there a name for this field of study? Specifically the study of how neural circuits are generated in the earliest stages, to lay down the high level structure of the brain before experience-based development can take over?

Answer 1

This is one of the most important question in neurosciences and we are far from understanding it. This is also the topic of the entire subfield of neurodevelopment (to answer your last question).

First, you are right that the exquisite degree and physiological correspondence between individuals of a species, and even between species, indicate a strong genetic component. But you are also right that we have good evidence for a developmental component to brains physiology. Here are a few random examples (at the top of my head, so maybe not the most important/influential papers):

• Cells selectivity in the primary visual cortex depends on visual experience. Animals housed in an environment with only horizontal or vertical stripes will have cells selective only to horizontal or vertical orientations (Blakemore & Cooper, 1970).

• At birth the primary visual cortex doesn't have cortical maps. They develop over time (e.g. Chapman, Stryker & Bonhoeffer, 1993).

• Due to synaptic pruning, newborn have actually more connections than later in life. These connections will be progressively eliminated during youth.

• Inserting a third eye in the forehead region of frogs makes connections to their optic tectum and creates columns of ocular dominance just as their normal 2 eyes (Constantine-Paton & Law, 1978). Even though having a 3rd eye is clearly not genetically encoded.

• Similarly, rewiring the retinal projections of ferrets to their auditory cortex will form orientation columns just as in the primary visual cortex (Sharma, Angelucci & Sur, 2000), even though this area usually processes a completely different modality.

• Putting amblyopic (a developmental visual disorder) rodents in complete darkness for some time seems to "reboot" their visual system and cure them from amblyopia (He, Ray, Dennis & Quinlan, 2007).

• Efficient encoding of natural statistics mimics the response properties of cells in the nervous system (e.g. Olshausen & Field, 1996).

What these different experiments suggest is that the overall structure of the brain is genetically determined, but development is truly what shapes the function and selectivity of cells.

Blakemore, C., & Cooper, G. F. (1970). Development of the brain depends on the visual environment. Nature, 228(5270), 477-478.

Chapman, B., Stryker, M. P., & Bonhoeffer, T. (1996). Development of orientation preference maps in ferret primary visual cortex. Journal of Neuroscience, 16(20), 6443-6453.

He, H. Y., Ray, B., Dennis, K., & Quinlan, E. M. (2007). Experience-dependent recovery of vision following chronic deprivation amblyopia. Nature neuroscience, 10(9), 1134-1137.

Constantine-Paton, M., & Law, M. I. (1978). Eye-specific termination bands in tecta of three-eyed frogs. Science, 202(4368), 639-641.

Sharma, J., Angelucci, A., & Sur, M. (2000). Induction of visual orientation modules in auditory cortex. Nature, 404(6780), 841-847.

He, H. Y., Ray, B., Dennis, K., & Quinlan, E. M. (2007). Experience-dependent recovery of vision following chronic deprivation amblyopia. Nature neuroscience, 10(9), 1134-1137.

Olshausen, B. A. (1996). Emergence of simple-cell receptive field properties by learning a sparse code for natural images. Nature, 381(6583), 607-609.

Answer 2

I will not offer you a description of 'experience-independent' development, as this is not my area, but here is a view on what its limits are. Effectively I am answering:

How much of the brain is actually hard wired in this way and how much is open to experience-based development?

Where a brain area will form is determined by the genotype and the micro-environment that any particular cell faces during development. Or, put in other words, I am not aware of any study showing that experience during development can drastically alter the topography of the brain. The same goes for axons and dendrites of particular cells, although they exhibit higher flexibility after drastic manipulation of experience such as sensory deprivation within the early stages of postnatal development.

This means that inter-areal connections are hard-wired by development in the sense that the target areas of a brain area or particular cell are fixed. As an example, some thalamic neurons are predetermined to target the cortex and vice-versa. A way that experience can influence that fact is by destroying the connectivity between the two areas (e.g. monocular deprivation). But I would be extremely surprised if a study claimed that by some manipulation of experience during development the same portion of the thalamus that normally projects to the cortex now projected to a totally unrelated, distant area such as, say, the brain-stem.

It would seem to me that the extent to which the brain is "hard wired" depends on the species. Humans seem to have a lot more room for specialisation in life, whereas some animals don't exhibit much individuality, tending to follow very regular behavioural patterns that have no doubt evolved over time, subject to natural selection. [...] Am I right in associating this process with the phenomenon of "instinct", that is, "hard coded" behavioural patterns in animals which appear to be hereditary[?]

I would challenge you to support this claim by research, as it does not echo anything I know about the nervous system. If anything, primates just have relatively more room for connections in the cortex and the cerebellum even after taking into account their relatively larger brains. Thus, it's not that they are less "hard-wired", in the sense described above, but rather that they have an enormous potential for synaptic plasticity in two key areas of the brain associated with more complex behaviour. When you compare reasonably closely related vertebrates, you find that the phylogenetically ancestral areas are mostly shared and thus their "hard-wired" areas are very similarly connected. Hence, primates only put an extra layer of complexity on top of this ancestral pattern of connectivity by having more space for change.

In conclusion, only the "highways" of the brain are pre-determined during development. The actual connectivity is sculpted by experience. Since the overall layout does not change by experience, animals adapt to their environment mostly through small-scale, synaptic changes.

Answer 3

This is a cool question and while I'm not a neuro(bio)logist, I've tried to quickly look into this.

Basically what you are asking for is the part of the (human) connectome (this is what researchers call the map/data/... of neural connections), that is hard wired. You may want to take a closer look at the human connectome project, if anyone is going to have/find the answer to your questions, it's going to be them. This paper seems to describe the latest state of the project and this one focuses more on the connection between the connectome and genomics. Sadly both papers are pay-walled and I don't have any access to the Elsevier journals right now, so I can't give you more info than that.

Answer 4

Is there a name for this field of study? Specifically the study of how neural circuits are generated in the earliest stages, to lay down the high level structure of the brain before experience-based development can take over?

The short answer is the field is called "Axon guidance" as a subfield of developmental neuroscience. It essentially studies how early neurons send their projections (axons) to their broad target areas where they will make their connections (synapses). This process is programmed genetically and occurs by itself using "guidance cues" that literally direct their growth through the brain (attracting to some areas, repelling from incorrect areas). see [Ref .1]

After the broad axon pathways are set up, early experience/learning will shape the connections further so that useful ones are kept and non-useful ones degenerate.

It's amazing stuff, check out movies of live axons growing through the early developing brain [Ref. 2]. I was lucky enough to do my Ph.D. studying this phenomenon :)

[Ref .1]: Seminal review of the Molecular biology of axon guidance [Ref. 2]: Growth of axons figure