Neuronal activity patterns and sensory responses
depend strongly on behavioral state. Active
behavioral states are associated with enhanced
gain, the presence of fast cortical dynamics,
and a reduction in spontaneous activity. These
effects depend strongly on the activity of
specific GABAergic interneurons. Inactive
behavioral states like sleep are associated with
enhanced spontaneous activity, reduced response
gain, and slow cortical dynamics that are
temporally highly structured. Spontaneous
activity patterns are strongly implicated in
memory consolidation processes.
The Greek philospher
Heraclitus said – “No man ever steps in the same
river twice, for it's not the same river and he's
not the same man.” While neuroscientists have made
great progress in describing the average tendency
of neuronal activity in response to external
stimuli, there is enormous variability in the
neuronal reponses to the same sensory inputs, and
the brain continuously shows profound fluctuations
in behavioral state, from multiple sleep stages,
to relaxed wake states, to attentive or aroused
wake states. The functional implications and
mechanisms of brain states and neuronal
variability remain poorly understood. Man-build
intelligent systems like computers and robots
respond in a highly predictable way to the same
input, and are essentially always in the same
state (on or off). The brain’s responses to the
same sensory inputs are highly variable and
dependent on the behavioral state. Furthermore,
when the organism is resting, e.g. during sleep,
it exhibits spontaneous activity patterns that are
highly structured, and during which neurons can be
more active as compared to aroused states[2,3].
Average pupil diameters
is shown as a function of time around air puff
onset. The air puff arouses the animal without
inducing locomotor activity. Cortical dynamics
(LFP signal) change with arousal and show slow
waves in low-arousal state. Spontaneous activity
is suppressed during arousal period.
states – like sleep and arousal – are
characterized by several aspects: 1) They are
associated with particular neuronal dynamics,
which can be measured both at the network level
and through intracellular recordings. 2) They are
accompanied by specific neuromodulatory tone; 3)
The neurons respond in characteristic ways to
sensory stimuli; 4) They are associated with
specific behavioral performance levels and biases.
In general, the more
active wake states are characterized by the
presence of faster waves (beta and gamma, 15-90
Hz) in the neocortex, which are linked conscious
processing and attention, while inactive states
are characterized by large-amplitude slow
waves. It is thought that these slower waves
play a role in memory consolidation. Fast gamma
activity in sensory areas is positively modulated
by arousal, even in the absence of locomotor
activity, which depends strongly on the
activity of GABAergic interneurons[6,1].
We compare here V1
activity of control animals, and animals in which
there is a developmental disorder in GABAergic VIP
interneurons, which compose about 1% of cells.
Animals in which there is a dysfunction of VIP
interneurons do now show any modulation of firing
activity by behavioral state (locomotor
Active states are
general associated with an increase in
noradrenergic and cholinergic tone. These
neuromodulators are released through long-range
projections of neurons in specific nuclei in the
brain stem like the locus coeruleus and the
nucleus basalis, and these nuclei are in turn
activated by other nuclei of the ascending arousal
system. Because the activity of neuromodulatory
projection systems correlates very well with pupil
diameter, we can use pupil diameter as a readout
for arousal level during wakefulness[1,2]. To
understand the mechanisms underlying state
modulation of cortical activity patterns, it is
critical to advance our understanding of the
impact of these neuromodulatory subsystems.
Neuromodulators can affect pyramidal neurons
directly, but also have highly specific effects on
the GABAergic interneurons. We have shown that
state modulation depends critically on the
developmental integrity of VIP interneurons, which
are strongly affected by neuromodulators [1,5].
does state influence sensory processing
The way in which
neurons respond to sensory stimuli depends
strongly on arousal level. While spontaneous
activity is decreased by cortical arousal, the
gain of sensory responses increases [1,2].
Furthermore, noise correlations, which can be
detrimental to sensory coding, are reduced with to
arousal. The dynamic regime in which the cortex
operates – from fast fluctuations in the beta and
gamma range, or slow fluctuations – might make an
important contribution to these changes in
gain[1,6]. We are currently investigating whether
state makes a more important contribution to the
response gain for stimuli that enhance fast
cortical dynamics. We are furthermore
investigating whether modulating oscillations
without changing the neuromodulatory tone (through
optogenetic manipulations) alone can change the
gain of neuronal responses to sensory inputs, and
the behavioral output.
and memory formation
We are studying how the
activity during sleep resembles that of waking
activity. Our hypothesis is that spontaneous
activity in neocortex depends in a precise way on
previous waking activity and contributes to memory
consolidation. With newly developed
mathematical algorithms in our group, we can
perform powerful unsupervised clustering of
temporal patterns . We are examining the
structure and dimensionality of temporal patterns
during spontaneous activity, and how these
patterns depend on experience.
 McGinley MJ, Vinck
M, Reimer J, Batista-Brito R, Zagha E, Cadwell CR,
Cardin JA, McCormick DA. Waking State: Rapid
Variations Modulate Neural and
Neuron. 2015 Sep 23;87(6):1143-61. doi:
10.1016/j.neuron.2015.09.012. Review. PubMed PMID:
26402600; PubMed Central PMCID: PMC4718218.
 Vinck M,
Batista-Brito R, Knoblich U, Cardin JA. Arousal
and locomotion make distinct contributions to
cortical activity patterns and visual encoding.
May 6;86(3):740-54. doi:
10.1016/j.neuron.2015.03.028. Epub 2015 Apr 16. PubMed PMID: 25892300;
PubMed Central PMCID: PMC4425590.
 Steriade M,
Timofeev I, Grenier F. Natural waking and sleep
states: a view
from inside neocortical neurons. J Neurophysiol.
2001 May;85(5):1969-85. PubMed PMID: 11353014.
 Genzel L, Kroes MC,
Dresler M, Battaglia FP. Light sleep versus slow
wave sleep in
memory consolidation: a question of global versus
local processes? Trends Neurosci. 2014 Jan;37(1):10-9.
doi: 10.1016/j.tins.2013.10.002. Epub 2013 Nov 7. Review. PubMed PMID:
 Batista-Brito R,
Vinck M, Ferguson KA, Chang JT, Laubender D, Lur
G, Mossner JM,
Hernandez VG, Ramakrishnan C, Deisseroth K, Higley
MJ, Cardin JA.
Developmental Dysfunction of VIP Interneurons
Impairs Cortical Circuits. Neuron. 2017 Aug
10.1016/j.neuron.2017.07.034. PubMed PMID:
Central PMCID: PMC5595250.
 Fries P. Rhythms
for Cognition: Communication through Coherence.
Neuron. 2015 Oct 7;88(1):220-35. doi:
10.1016/j.neuron.2015.09.034. Review. PubMed PMID: 26447583; PubMed Central
 Grossberger, L., Battaglia, F, Vinck, M. Unsupervised clustering of temporal
patterns in high-dimensional neuronal
ensembles using a novel dissimilarity measure.