| dc.description.abstracteng | VIP expressing interneurons are an essential component of cortical circuitry. This
distinct subgroup of inhibitory interneurons was always described as the most
heterogeneous subgroup of inhibitory interneurons. However, little is known about
the precise structure of this heterogeneity and whether these neurons nevertheless
form distinct subgroups on the basis of their characteristic properties. This question
was addressed in this work by targeting genetically-labeled VIP neurons in acute
thalamo-cortical section of the barrel cortex in mice. Based on whole cell patch-clamp
experiments, the electrophysiological profile of VIP neurons was characterized. Their
morphology was reconstructed and quantified subsequently if neurons were labeled
sufficiently. Additionally, responses to NA, ACh, and 5HT were recorded to access
information about the sensitivity of VIP neurons to neuromodulation. Receptors
mediating the responses to ACh and 5HT were identified in pressure application
experiments in conjunction with antagonists for certain receptor subtypes. The
analysis of the electrophysiological profile of VIP neurons confirmed the previously
observed heterogeneity. To describe this heterogeneity in detail, firing patterns were
quantified using a novel method that included not only their adaptation rates but also
the current dependency and frequency spectrum. These important features allowed
an observer-independent description of the firing behavior of VIP neurons and also
generated insight into AP waveforms and passive properties of these neurons. Based
on these data, VIP neurons could be subdivided into 5 electrophysiological types. The
distribution profile of these types throughout the barrel cortex unveiled that bursting
VIP neurons were exclusively found in layer II/III with a tendency towards upper layer
II/III. In contrast, CA VIP neurons of low frequency (one of the 5 electrophysiological
types) were found predominantly in lower layer II/III and layers IV-VI. The three
remaining types were found intermingled throughout all layers of the barrel cortex. The
location preference of bursting VIP neurons was partially reflected in the morphology
of VIP neurons. Although a clear definition of subtypes was ambiguous due to the low
number of recovered neurons, differences in the organization of dendritic trees became
apparent in lower layer II/III. Here, VIP neurons spread their dendrites towards layer
Va, whereas in upper layer II/III VIP neurons restricted their dendrites to layers I and
II/III. In conjunction with the distribution profile of electrophysiological types, bursting
VIP neurons seem to have a different laminar input domain than low frequency CA VIP
neurons. Furthermore, the morphology of the few reconstructed neurons from layers
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IV-VI indicates that their domains of input and output greatly differ in comparison to VIP
neurons from layer II/III: in deeper layers of the cortex, the dendrites of VIP neurons
are found in all layers, whereas their axon is virtually restricted to layers V and VI.
In contrast, VIP neurons from layer II/III restrict their dendrites to superficial layers
I-IV and spread their axon into all layers of the barrel cortex. These morphological
differences suggest a differential involvement into cortical circuitry. In layer II/III,
VIP neurons are depolarized by NA, ACh, and 5HT confirming earlier studies. The
depolarization induced by ACh is mediated by nicotinic non-α7 ACh receptors in all
tested VIP neurons. Interestingly, responses to 5HT are mediated by 5HT2R in all VIP
neurons but 5HT3aR mediated currents were only observed in 46% of all tested VIP
neurons identifiable by a biphasic response pattern. The depolarization induced by
ACh and 5HT was sufficient to trigger a switch in the firing behavior of 20% of all VIP
neurons: bursting VIP neurons. Their firing pattern switches from bursting to a more
tonic CA-like when their membrane potential is depolarized. This firing behavior was
never described for VIP neurons before and suggests an additional specialization to
integrate brain states. In conclusion, VIP neurons eluded a precise classification which
integrates all aspects of their electrophysiology, morphology, and neuromodulation.
However, the description of VIP neurons provided in this work serves as a foundation
to integrate observations from past and future studies. | de |