Ivy Cells: A Population of Nitric-Oxide-Producing, Slow-Spiking GABAergic Neurons and Their Involvement in Hippocampal Network Activity

Abstract

In the cerebral cortex, GABAergic interneurons are often regarded as fast-spiking cells. We have identified a type of slow-spiking interneuron that offers distinct contributions to network activity. "Ivy" cells, named after their dense and fine axons innervating mostly basal and oblique pyramidal cell dendrites, are more numerous than the parvalbumin-expressing basket, bistratified, or axo-axonic cells. Ivy cells express nitric oxide synthase, neuropeptide Y, and high levels of GABA(A) receptor alpha1 subunit; they discharge at a low frequency with wide spikes in vivo, yet are distinctively phase-locked to behaviorally relevant network rhythms including theta, gamma, and ripple oscillations. Paired recordings in vitro showed that Ivy cells receive depressing EPSPs from pyramidal cells, which in turn receive slowly rising and decaying inhibitory input from Ivy cells. In contrast to fast-spiking interneurons operating with millisecond precision, the highly abundant Ivy cells express presynaptically acting neuromodulators and regulate the excitability of pyramidal cell dendrites through slowly rising and decaying GABAergic inputs.

Expression of COUP-TFII Nuclear Receptor in Restricted GABAergic Neuronal Populations in the Adult Rat Hippocampus

“…In the current study, we defined two further differences. First, neurogliaform cells preferentially discharged at the peak of theta oscillations recorded in stratum pyramidale, whereas ivy cells discharged at the trough of theta waves (Fuentealba et al, 2008b), similar to other interneurons that innervate strata radiatum and oriens, like bistratified, double projection and trilaminar cells (Klausberger and Somogyi, 2008). Further in vivo recordings from identified neurogliaform cells will be necessary to confirm this conclusion based at present on two cells.…”

“…Our anatomical characterization of the GABAergic cells indicates that 80–90% of COUP-TFII expression is accounted for by interneuron-selective interneurons (~40–45%), ivy cells (~30–35%) and neurogliaform cells (~10%). Ivy cells were described earlier (Fuentealba et al, 2008b), and partial information was reported for enkephalin-expressing interneuron-selective interneurons immunopositive for COUP-TFII (Fuentealba et al, 2008a). Here we have established that radiatum-retrohippocampal projection cells, subpopulations of CB- and CCK-expressing cells (Klausberger et al, 2005; Jinno et al, 2007), as well as neurogliaform cells comprise the COUP-TFII-expressing interneurons.…”

“…However, other COUP-TFII-expressing cells such as ivy, enkephalin-expressing, or radiatum-retrohippocampal cells tend to fire at or close to the trough of theta (Fuentealba et al, 2008a,b; Jinno et al, 2007). Therefore, the theta firing phase is not uniform across COUP-TFII-expressing neurons and may depend on their synaptic connectivity in the network.…”

Interneuronal GABAA receptors inside and outside of synapses

“…Ontogenetically, NGFCs/IvyCs originate from two sources: the 5HT 3A -R+, reelin+ NGFCs/IvyCs derive from the caudal ganglionic eminence (CGE), whereas nNOS+ NGFCs/IvyCs are born in the MGE [45,66,67]. NGFCs/IvyCs release GABA slowly and diffusely, hence have been implicated in GABAergic volume transmission [42], but may also play a role in the dynamics of the θ rhythm [68–72]. In the hippocampus they are mostly localized in the str.…”

Cortical NO interneurons: from embryogenesis to functions

“…By using an elegant spectral analysis to improve recognition of immunofluorescently labeled nNOS and neuropeptide-Y (NPY) expressing neurons (Somogyi et al, 2012), found that most NO interneurons with soma in the stratum radiatum of the CA1 area exhibit characteristic properties of ivy cells and express NPY. In contrast to their counterparts in the stratum pyramidale (Fuentealba et al, 2008), stratum radiatum ivy cells display a different pattern of axonal and dendritic arborizations suggesting that these two subpopulations of hippocampal NO interneurons are involved in different microcircuits.…”