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European Journal of Neuroscience
European Journal of Neuroscience, Vol. 33, pp. 1018–1024, 2011
Seven principles in the regulation of adult neurogenesis
Gerd Kempermann
CRTD – Center for Regenerative Therapies Dresden, and DZNE, German Center for Neurodegenerative Diseases, Dresden,
Keywords: dentate gyrus, hippocampus, learning, plasticity, stem cell
Seven key elements describing the regulation of adult neurogenesis are proposed. (i) A distinction must be made between regulation
and ‘control’ at the transcriptional level in order to appreciate the hierarchy of regulatory factors. (ii) The regulatory hierarchy
comprises conceptual levels from behaviour to genes. Consequently, ‘regulation’ of neurogenesis can be confounded by confusing
rather than integrating factors, levels and concepts. The immense spectrum of neurogenic regulators reflects the sensitivity of adult
neurogenesis to many different types of stimuli, and provides a means of abstraction. (iii) Age per se does not seem to play a
constant role in the modulation of this process, as the dramatic ‘age-related’ changes in adult neurogenesis only take place early in
life. (iv) The regulatory hierarchy at any given time-point is corresponded by the directionality and sequential interdependence of
different regulatory factors in the course of development. Regulation goes from non-specific to specific, and the following steps build
on regulation at the previous ones. (v) This complexity is reflected at the genetic level in that adult neurogenesis is highly heritable
and highly polygenic with single factors explaining little of the variance. (vi) As regulation is additive, there is an element of selfreinforcement in the regulation of adult neurogenesis, allowing the formation of regulatory reserves for situations of functional
demand. (vii) The complexity of regulation makes adult neurogenesis sensitive to pathological disturbance at various levels,
suggesting that different molecular events might result in similar and shared behavioural or functional phenotypes originating in the
dentate gyrus.
Adult hippocampal neurogenesis attracts so much attention and
interest because it has become increasingly clear that the new neurons
exert critical functions in the hippocampus and help in explaining
particular aspects of learning and memory (Becker & Wojtowicz,
2007; Kempermann, 2008; Appleby & Wiskott, 2009; Garthe et al.,
2009; Aimone et al., 2010). Most of the roughly over 3000
publications to date found in PubMed, however, are concerned with
the regulation of adult neurogenesis. One underlying assumption is
that knowing about how adult neurogenesis is regulated would also
provide insight into its relevance and support the idea of its functional
significance (Johnson et al., 2009; Mu et al., 2010; Pathania et al.,
2010). Indeed, historically, the observation that adult neurogenesis is
regulated by behavioural activity was taken as the first key argument
that neurogenesis is more than an atavism but directly tied to
(ethologically relevant) behaviour (Gage et al., 1998).
‘Regulation’, nevertheless, is a rather elusive term, and so far there
have been few attempts to systematically address what is known about
the regulation of adult neurogenesis. Given the vast number of papers,
one key goal for the field should be to develop integrating views on
the mechanisms by which adult neurogenesis is regulated and the
reciprocal relationship between regulation and function. The sheer
Correspondence: Dr G. Kempermann, as above.
E-mail: [email protected]
Received 22 September 2010, revised 30 November 2010, accepted 14 December 2010
number of factors that seem to ‘regulate’ adult neurogenesis suggests
that, if the regulation is not random, some overarching principles must
The present brief review highlights seven principles of how adult
hippocampal neurogenesis is regulated, and attempts a conceptual
view rather than reviewing, again, individual factors. In the end, a
potentially unifying concept remains to be identified, but the seven
principles listed here, which are by no means exclusive, underscore
important aspects that need to be appreciated if the unifying theory is
Principle #1: Adult neurogenesis is regulated, whereas
embryonic neurogenesis is controlled
The distinction between ‘regulation’ and ‘control’ might sound like a
semantic issue only, and in fact the terms are often used synonymously. But if regulation is seen as a deviation from a baseline, which
is maintained by an intrinsic control, the difference becomes relevant.
If considering individual factors with regards to their influence on
adult neurogenesis, mechanisms that maintain the baseline level of
neurogenesis fall into substantially different classes than those far
more numerous factors that regulate neurogenesis beyond that
baseline. The latter category is essentially absent in the embryonic
brain, where neurogenesis is to a much larger degree determined by
genetic programs. Activity-dependent regulation is found during foetal
brain development, but is obviously less influential than after birth,
ª 2011 The Author. European Journal of Neuroscience ª 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
Regulation of adult neurogenesis 1019
Principle #2: Regulation of adult neurogenesis can be
described at several conceptual levels, but is ultimately
related to behaviour and function on one side and control
on the other
The argument from Principle #1 can be taken one step further. Adult
neurogenesis is about plasticity, and plasticity is the reciprocal
interaction between structure and function. There is no plasticity
without the appropriate interaction with the outer world that provides
the appropriate trigger. Brain activity and behaviour have no or little
influence on the backbone process of adult neurogenesis, they rather
influence quantity and quality at different stages of development by
interacting with the underlying neurogenic programs.
The implication of this insight is that – ultimately – all actual
regulation of adult neurogenesis (as opposed to control) will be the
consequence of and thus be dependent on behavioural activity or
external stimuli. The individual pieces of information about regulation
that we gather must always be seen within this extended context. They
are positioned in a high-dimensional vector space defined by
transcriptional control and behaviour.
of individual
T cells
when the individual begins interacting with the outer world. Many
molecular mechanisms that govern embryonic brain development are
also relevant for adult neurogenesis. For example, the sequence of
transcription factors known from cortical development: Pax6 –
Neurog2 – Tbr2 – Neurod1 – Tbr1, is also found in the neurogenic
niches of the adult brain (Hodge et al., 2008; Brill et al., 2009).
Signalling in the Wnt, Shh, Bmp and Notch systems similarly plays
the expected important role. Disturbance in the backbone of control
causes severe defects and abortive neurogenesis. Without these ‘usual
suspects’ of neuronal development, no (adult) neurogenesis occurs
(Lim et al., 2000; Lie et al., 2005; Breunig et al., 2008; Lugert et al.,
2010), but for exactly that reason they often tell us little about the
particularities of adult neurogenesis as opposed to neurogenesis in
Many known ‘regulators’ of adult neurogenesis, in contrast, are of
less relevance for embryonic brain development. Interference with
them reduces neurogenesis or alters its quality, but usually does not
abolish it altogether. Examples are the acetylcholinergic input to the
dentate gyrus from the medial forebrain (Cooper-Kuhn et al., 2004;
Mohapel et al., 2005; Cohen et al., 2008) or the serotonergic system
(Brezun & Daszuta, 1999; Santarelli et al., 2003; Banasr et al., 2004;
Klempin et al., 2010), hormones (Cameron & Gould, 1994; Shingo
et al., 2001; Lichtenwalner et al., 2006), or endogenous psychotropic
systems, like the endocannabinoids (Wolf et al., 2010) or the
endorphins (Eisch et al., 2000). Knockout of the enzyme tryptophanehydroxylase 2, for example, eliminates all serotonin in the brain,
but the animals have a remarkably mild developmental phenotype and
can reach adulthood (Alenina et al., 2009), although serotonin plays
important roles in many regulatory events. This is not to say that
interfering with such factors would generally not have any phenotype
in embryonic brain development (they indeed have), but the more
remote the mediators are from the transcriptional level and the more
their own regulation depends on brain activity and behaviour, the less
dominant is the result for the overall process. The boundary between
more or less extrinsic regulators and the transcription factors and other
parts of the genetic machinery that execute their programmed action is
obviously blurred because any extrinsic factor must ultimately act on
an intrinsic system via intermediate messenger systems, and epigenetic mechanisms affect transcription of the genome as do transcription factors. But the distinction helps to see the complexity of
neurogenic regulation and control, which is much more than
immediately meets the eye of the observer in an altered ‘number of
BrdU-positive cells’.
When we study embryonic neurogenesis we are mostly interested in
how the complex brain structure that we see in the adult has
developed. Exploring adult neurogenesis, in contrast, means studying
development under the conditions of the adult brain, in which
development has otherwise largely ceased and in which neurogenesis
has turned into an adaptive mechanism. This implies in other words
that ‘control’ rather stands for original development, but regulation for
plasticity on the basis of that development. One cannot understand
adult neurogenesis without embryonic neurogenesis; but even knowing all about embryonic neurogenesis one will miss the particular
complexity in the regulation of adult neurogenesis (Fig. 1).
The distinctions, and thus the point of making them, have their
limitations. Maintaining a homeostatic balance in a cell requires both
control and regulation. But for understanding the particularities of
adult neurogenesis it remains important to note that it is more than the
control of neuronal development under the conditions of the adult
Adult neurogenesis
Fig. 1. The cloud of regulation is large and not homogenous. It is helpful to
conceptually distinguish between the numerous and heterogenous factors that
regulate adult neurogenesis and those rather few indispensable ones that
actually control it at the transcriptional level. Ways have to be identified to
conceptually put regulatory events into hierarchies and systematic relationships
(see also Fig. 2). Mentioned regulators are examples only – no specific
relationships are implied in the figure. BDNF, brain-derived neurotrophic
factor; FGF2, fibroblast growth factor 2; GABA, c-aminobutyric acid; GH,
growth hormone; IGF1, insulin-like growth factor 1; IL6, interleukin 6; LTP,
long-term potentiation; NT3, neurotrophin 3; VEGF, vascular endothelial
growth factor.
ª 2011 The Author. European Journal of Neuroscience ª 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 33, 1018–1024
1020 G. Kempermann
An increasing number of studies is taking this principle into account
by including one of the experimental paradigms of behavioural
activity with known influence on adult neurogenesis, for example
environmental enrichment and voluntary wheel running, into their
study of how a particular candidate gene might affect adult
neurogenesis (Feng et al., 2001; Cao et al., 2004; Corsini et al.,
2009; Gobeske et al., 2009; Lugert et al., 2010). Ultimately, research
on adult neurogenesis is hardly ever about the baseline, which is more
or less just the transposition of the embryonic principles to the
conditions of the adult brain, but about how well adult neurogenesis
can perform its specific role in functionally relevant plasticity.
The term regulation is so elusive, because it encompasses mechanisms from behavioural to molecular, which stand in a hierarchical
relationship and form large and complex networks of interdependencies (Fig. 2). Whether one sees the genes at the top or bottom of that
hierarchy matters little. Individual mechanisms of regulation might fill
one or a few papers, but will always raise questions about their
integration into the bigger picture. Obviously, regulation does not only
occur by means of gene transcription. There are numerous posttranscriptional and post-translational regulatory events, which, however, ultimately must be programmed at the genetic level, too.
The list of potential regulators of adult neurogenesis at all levels is
long and continues to grow. What does it tell us, if so many different
factors regulate neurogenesis and ultimately seem to have so similar
consequences? It seems that adult neurogenesis is extremely sensitive
to external stimuli. But this in turn might exactly be the point – the
highly converging regulation, ultimately linked to behaviour, is a
means of fine-tuning the plastic response provided by the new
neurons. The immense width of regulatory mechanisms is a means of
‘listening to the world’. Adult neurogenesis can respond to numerous
Social context
Growth factors
Spatial Learning
Neurotrophic factors
Dentate gyrus
Paracrine signaling
Gap junctions Niche
signaling Cytoplasm
different conditions, when these are translated into some sort of
molecular signature. This only makes sense if a meaningful integration
over all these various inputs can take place. Regulation of adult
neurogenesis would thus be a kind of abstraction, being able to
appropriately fine-tune the production of new neurons to many
different situations, and the surprisingly large number of potential
regulators would reflect this openness at the molecular level.
Regulation in this context closes the circle of plastic responses to
the world (Fig. 3).
Principle #3: Adult neurogenesis is not regulated by age
From the fact that many new neurons are produced in young animals
and very few at old age, we have concluded that adult neurogenesis
decreases with age and that age itself would be a potent, if not the
most potent, negative regulator of adult neurogenesis (Kuhn et al.,
1996; Kempermann et al., 1998; Ben Abdallah et al., 2010). It even
seems that the ‘age-dependent decline’ has become a conceptual
cornerstone of adult neurogenesis research. Generally, age would be a
regulatory factor like no other, thus deserving particular highlighting.
Passing of time affects all regulatory and controlling events. However,
at least in rodents and humans, adult neurogenesis only decreases
dramatically during a time, when – strictly speaking – it should not
even be called truly ‘adult’ – childhood and adolescence (Ben
Abdallah et al., 2010; Knoth et al., 2010; Fig. 4). In mice, dentate
gyrus neurogenesis peaks at about postnatal day 8, and in terms of the
processual characteristics transforms to ‘adult neurogenesis’ at about
postnatal day 15. A mouse is ‘adult’ by many definitions not earlier
than at least a week later. At 3 months, when the mouse is ‘adult’ by
most standards, neurogenesis is already very low compared with
postnatal levels, but hippocampal neurogenesis remains at a very low
level for the remaining time of life. The one existing estimate for
humans, even though only based on the number of doublecortinexpressing cells as surrogate measure, shows a very similar pattern
(Knoth et al., 2010). The characteristic early decline is often taken as
evidence that adult neurogenesis is ‘regulated’ by age, but for the most
part of life no such ‘regulation’ exists. The data rather suggest that in
rodents and primates beyond childhood or young adulthood levels of
adult neurogenesis are generally quite invariant to age.
The early steep loss in precursor cell proliferation and, hence, the
potential for neurogenesis can be counteracted by, for example,
physical activity (Kronenberg et al., 2006). Activity early in life could
thus translate to a greater potential for plasticity in old age by
maintaining the baseline at a higher level or at least postponing the
decline. Experiencing old age as a chance for novel learning
experiences might depend on preventive measures at a much younger
age. If that window of early opportunities has been missed, the curve
of possible changes in neurogenesis remains rather flat for the
remaining time of life. This would be different if age was a regulator
of neurogenesis with a linear effect across the lifespan.
Fig. 2. Regulation is hierarchical. Regulation occurs at numerous levels, from
behaviour in a social context down to the genes. Although ultimately all
regulation must somehow relate to genetic code, there are numerous posttranscriptional and post-translational regulatory events that contribute to the net
effect. Many ‘regulators’ affect several hierarchical levels (e.g. neurotransmitters). The hierarchies thus structure the ‘cloud’ of Fig. 1, but they are deceiving
because the structure of the ‘regulatory space’ is far more complex than simply
layered. Still, even if details are difficult to grasp, regulation is hierarchical and
must be conceptualized as such in order to allow deeper conclusions about
‘regulation’ and ‘control’. LTP, long-term potentiation.
Experience of the
environment; learning
Behavior in the
Adult neurogenesis
Adapted hippocampal
Fig. 3. Plasticity means a feedback loop between structure and function,
mediated by regulation.
ª 2011 The Author. European Journal of Neuroscience ª 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 33, 1018–1024
250 000
200 000
150 000
6 weeks
9 months 12 months 24 months
100 000
50 000
Fig. 4. Adult neurogenesis is not regulated by age. For most of the lifespan
adult neurogenesis is at a rather constant, very low level. Very high levels of
‘adult’ neurogenesis are found at times, when the individual is not yet truly
adult. The numbers in the figure reflect doublecortin (DCX)-expressing cells
per section area of the human hippocampus, obtained from 54 post mortem
samples and replotted here from Knoth et al. (2010). Doublecortin expression
is only a rough proxy of ‘neurogenesis’, but can be addressed in humans. Inset
– a similar picture can be drawn for rodents (McDonald & Wojtowicz, 2005;
Kronenberg et al., 2006; Ben Abdallah et al., 2010). In many cases, the slope
of the decline is even steeper than shown in this example. The rodent data are
reprinted from Kronenberg et al., ‘Physical exercise prevents age-related
decline in precursor cell activity in the mouse dentate gyrus’, Neurobiology of
Aging, Vol. 27, pp. 1505–1513, Copyright 2006, with permission from Elsevier.
Principle #4: Regulation of adult neurogenesis at multiple
stages of development is additive and later stages are
dependent on previous ones
Historically, the term ‘neurogenesis’ stood essentially for the proliferation of those precursor cells during embryonic brain development,
whose progeny would become neurons (e.g. Altman, 1969). This
restricted use was not exclusive, but became implicit in many
statements about the generation of new neurons in the adult brain.
Several studies only measured precursor cell proliferation, and
equalled this measurement with the generation of new neurons. For
the reasons stated in Principles #1 and #2, however, this would only
make sense if precursor cell proliferation would indeed be strictly
indicative of the net result at the level of functionally integrated new
neurons. But this is not the case (Kempermann et al., 1997, 2006).
During infancy of the field of adult neurogenesis research in the
1990s, it still seemed unorthodox to consider ‘neurogenesis’ as a
process and not as an event. But the generation of neurons cannot be
reasonably subsumed under single stages of that process that do not
faithfully represent the end result. The processual nature of adult
neurogenesis has the consequence that net regulation depends on
influences at many different stages of neuronal development. Three are
covered in most reports on adult neurogenesis: precursor cell
proliferation; survival of newborn cells; and phenotypic differentiation; but numerous others have been identified.
These stages are not independent of each other. Development is
essentially unidirectional, and later stages build upon preceding ones.
Cells that have not been generated in the first place cannot undergo
modifications in maturation, migration, dendritic arborization, integration, etc., but those cells that have been produced can become
subject to a large number of potential regulatory stimuli. Consequently, the individual impact of regulation and the latest stages of
development will be quantitatively small but highly specific. Regulation at the beginning at early stages, most notably precursor cell
proliferation, will be less specific. With each potentially regulatable
step the framework for the regulation of the following stages shifts and
the conditions change. Presumably, fewer factors affect the latest, most
specific stages than the non-specific early ones (Fig. 5). The
directionality and sequential dependence of regulatory events in the
course of neurogenesis substantially complicate models and theories
of how adult neurogenesis is regulated, but lie at the heart of the entire
Voluntary wheel running prominently induces precursor cell
proliferation, which in very acute settings does not lead to an increase
in net neurogenesis (Steiner et al., 2008). Continued exercise lets the
pro-proliferative response wear off, but now a second effect sets in –
neurogenesis at later stages continues to rise, even when proliferation
has already returned to baseline (Kronenberg et al., 2003; Snyder
et al., 2009). A pro-survival stimulus (e.g. by exposure to an enriched
environment) settled upon the running-induced proliferation increases
this secondary effect of running on later stages of neuronal development (Fabel et al., 2009). The effects become additive. This implies
that, although proliferation is not a good predictor of net neurogenesis,
a greater potential for neurogenesis due to increased precursor cell
proliferation enhances the response to a stimulus that affects primarily
later stages.
Principle #5: Adult neurogenesis is a quantitative,
polygenic trait
The consequence of Principle #4 is that there is no master switch and
no ‘neurogenesis’ gene, whose manipulation would suffice to regulate
(and control) adult neurogenesis. In genome-wide mapping studies,
individual gene loci explain very little variance, although the overall
heritability is fairly high (at least in the genetic reference populations
chosen; Kempermann et al., 2006; Poon et al., 2010).
Single gene studies, which obviously remain necessary to study
potential contributions of individual factors, tend to obscure this fact
and might lead to paradoxical results. Several studies have, for
example, shown that interfering with different individual candidate
signalling pathways could abrogate the exercise-induced increase in
Number of possible regulators
Number of DCX-positive cells per area
dentate gyrus [mm2]
Regulation of adult neurogenesis 1021
fate choice
Cell cycle exit
Fig. 5. Preceding regulatory events limit the range of possible following steps.
In the course of neuronal development, the influence of regulatory events at
later stages is limited by the range of options left by decisions at previous
stages. Overall, the width of regulation decreases. Regulation at later stages
builds upon the foundation laid at earlier stages.
ª 2011 The Author. European Journal of Neuroscience ª 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience, 33, 1018–1024
1022 G. Kempermann
precursor cell proliferation and neurogenesis [vascular endothelial
growth factor (VEGF; Fabel et al., 2003), insulin-like growth factor
(IGF)1 (Trejo et al., 2001), Akt1 (Bruel-Jungerman et al., 2009), bone
morphogenic proteins (BMPs) (Gobeske et al., 2009), cannabinoid
receptor 1 (Wolf et al., 2010), etc.]. At face value, some of these
results seem mutually exclusive – if VEGF is blocked, IGF1 should be
sufficient to do the job. This particular paradox has not been formally
resolved. The solution might lie in the combination of the poor
resolution of our experiments with respect to measuring adult
neurogenesis and the complexity of the regulation. In the above
example, Akt1 would lie downstream of both VEGF and IGF1,
linking both pathways but without any guarantee that either factor
might not also affect additional, independent pathways (BruelJungerman et al., 2009). Intracellular regulatory pathways form
complicated networks of direct and indirect interactions, which – as
outlined above – change with time. Their convergence on the control
mechanisms of adult neurogenesis might themselves be subject to
modulation in some sort of ‘meta-regulation’. In principle, the laws of
these interaction networks should be understandable and a higherorder description of ‘regulation’ be possible.
The natural balance in these systems or networks can be disturbed at
different levels, provoking compensatory changes at others. The same
applies to the sequence of events in the course of adult neurogenesis.
This leads to testable hypotheses: how does, for example, precursor
cell proliferation respond, when survival is affected? At a more
mechanistic level, such analyses will become considerably more
complicated due to the hierarchical and combinatorial influence of
diverse regulators. For example, how do the effects of regulatory key
factors like brain-derived neurotrophic factor on precursor cells and
their progeny change when there is more serotonin around or when the
Wnt pathway is dampened? No single regulator is independent.
One can obviously push this argument to triviality. Systems biology,
as the scientific answer to such complexity is called, has sometimes a
questionable reputation because complexity per se is no answer to the
question of regulation (Wolkenhauer & Ullah, 2007). Science is, after
all, the art of complexity reduction. But the issue is, how far this
reduction needs to be taken. Here the answer is that very reductionistic
experiments will miss key components and might generate contradictory results. So, while the full complexity might be impossible to
capture and understand, more integration is needed than can ultimately
be provided by summing up individual single-gene studies.
Principle #6: Regulation of adult neurogenesis is selfreinforcing
The observation that regulation of adult neurogenesis can be additive
suggests that if neurogenesis continues to be regulated over time further
regulation will be facilitated. The entire activity-dependent regulatory
mechanism obeys a use-it-or-lose-it rule. In other words, it is plastic
itself. At this point, age comes back into the equation, but not as a
negative regulator, rather as an opportunity. Older animals that have
experienced a lot would have retained more responsive neurogenic
machinery in the adult hippocampus but would actually require less
regulation, because the network adaptation that can be achieved by adult
neurogenesis is cumulative. The ‘neurogenic reserve’ provided by a
maintained precursor cell pool in the aging hippocampus (Kempermann,
2008) must have a correspondent at the level of regulation – there must
be a regulatory reserve as well. The concept of plasticity implies a
feedback loop, which in this case includes adult neurogenesis and its
regulation (Fig. 3; For an updated discussion of the neurogenic reserve
hypothesis, see Kempermann et al., 2010).
Principle #7: Regulation of adult neurogenesis can fail in
complex ways
If embryonic development fails, severe malformations with broad
functional implications (or even death) are the consequences. If only
‘adult’ neurogenesis fails, this results in a deficit in cellular plasticity
in one single neuronal network and will impair the function of the
hippocampus. The dentate gyrus still retains its usual form, and in
most cases its general network structure; it might be smaller, but given
the immense natural variation in dentate gyrus size this will be difficult
to assess in individuals. Other defects might be more qualitative in
nature, not changing cell numbers and gross regulation at all, but
resulting in problematic connectivity. If the current ideas about the
functional relevance of adult-born neurons hold, the functional
consequences of adult neurogenesis are specific and precisely defined.
Consequently, a great number of misregulations might ultimately
result in very similar functional phenotypes at the level of the dentate
gyrus. This is thus, in other words, the pathological flip side of
Principle #2. If the functional contribution of adult neurogenesis is
indeed as fundamental as we assume and the broad spectrum of
potential regulators reflects the sensitivity of the system, a great
number of pathological events interfere with neurogenesis-based
cognitive and affective function; regulatory sensitivity has its price.
Concluding remarks – the eighth principle
The number of principles – seven – was chosen deliberately. The list is
not meant to be – and cannot be – exhaustive, but the choice of just
seven principles was also not far-fetched and the scope of the
mentioned ideas covers substantial ground. But one final principle that
has been shining through this text and somehow cuts across the others
needs to be mentioned again. In the end, all regulation of adult
neurogenesis has to be seen in its relation to function. At diverse
points of this article we have alluded to this fact. Regulation of adult
neurogenesis occurs to achieve, maintain, modify or improve the
function of: (i) the new neurons; (ii) the dentate gyrus; (iii) the
hippocampus; (iv) the brain; and (v) the individual (and the list is not
complete). There is a seamless transition from the function of the cell
to the behaviour of the individual. Function is thus something like the
overarching eighth (or thus – first) principle. But as little as regulation
can be captured in one simple concept, function is something generic.
Adult neurogenesis satisfies very specific functional needs. Adult
neurogenesis is the solution that evolution found to solve a particular
functional challenge, which we have not yet fully understood. We will
not extend this question here, but one day in the not so far future a
review article ‘Seven principles in the function of adult hippocampal
neurogenesis’ should be possible. It is safe to predict that a principle
referring to the complex and activity-dependent regulation of adult
neurogenesis will be part of such an overview.
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