Limits...
Dynamic functions of GABA signaling during granule cell maturation.

Dieni CV, Chancey JH, Overstreet-Wadiche LS - Front Neural Circuits (2013)

Bottom Line: Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region.Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages.We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.

ABSTRACT
The dentate gyrus is one of the few areas of the brain where new neurons are generated throughout life. Neural activity influences multiple stages of neurogenesis, thereby allowing experience to regulate the production of new neurons. It is now well established that GABA(A) receptor-mediated signaling plays a pivotal role in mediating activity-dependent regulation of adult neurogenesis. GABA first acts as a trophic signal that depolarizes progenitors and early post mitotic granule cells, enabling network activity to control molecular cascades essential for proliferation, survival and growth. Following the development of glutamatergic synaptic inputs, GABA signaling switches from excitatory to inhibitory. Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region. Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages. We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability.

No MeSH data available.


Related in: MedlinePlus

GABAergic innervation in adult neurogenesis. Cartoon depiction of the stages of GC maturation highlighting the sequence of interneuron innervation. Progressive stages of GC maturation are indicated by the blue cells. Select interneurons and their axonal targeting regions are indicated by the corresponding shaded areas (red, PV+ basket cells; green, Ivy/NG cells; orange, axo-axonal cells). The shift in function of GABA signaling from excitation to inhibition, and the sequence and modes of signaling from interneuron subtypes are indicated in the gradient bars below. The sequence of innervation by numerous other dentate interneuron subtypes [reviewed in Houser (2007)] is not yet known so not included. SGZ, subgranule zone; GCL, granule cell layer; ML, molecular layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3539683&req=5

Figure 1: GABAergic innervation in adult neurogenesis. Cartoon depiction of the stages of GC maturation highlighting the sequence of interneuron innervation. Progressive stages of GC maturation are indicated by the blue cells. Select interneurons and their axonal targeting regions are indicated by the corresponding shaded areas (red, PV+ basket cells; green, Ivy/NG cells; orange, axo-axonal cells). The shift in function of GABA signaling from excitation to inhibition, and the sequence and modes of signaling from interneuron subtypes are indicated in the gradient bars below. The sequence of innervation by numerous other dentate interneuron subtypes [reviewed in Houser (2007)] is not yet known so not included. SGZ, subgranule zone; GCL, granule cell layer; ML, molecular layer.

Mentions: Adult neurogenesis encompasses the proliferation, differentiation, and maturation of new GCs that are continually added to the dentate. The continuum of neuronal development can be simplified into the stepwise progression of neural stem cells (Type I cells) into progenitors (Type II cells), differentiation of post mitotic newborn neurons, and the synaptic integration of immature GCs, with each stage exhibiting different physiological properties [Figure 1; reviewed by Mongiat and Schinder (2011)]. The absolute number of cells generated each day depends on rodent age and species, with estimates ranging between 2000 and 9000 under basal conditions (Kempermann et al., 1997b; Cameron and McKay, 2001). Adult generated neurons that survive the first few weeks following cell birth are likely to persist long term (Dayer et al., 2003), allowing adult generated neurons to accumulate over time, potentially achieving up to 10% of the total granule cell population (Lagace et al., 2007; Imayoshi et al., 2008). Yet the majority of newly generated cells undergo apoptosis within the week after division (Hayes and Nowakowski, 2002; Sierra et al., 2010), resulting in a population of immature neurons that is a small percentage of the total population of GCs. In young adult mice, it has been estimated that ~10–12 day-old GCs comprise about 3% of the population (Pugh et al., 2011) and 4-week old immature GCs comprise <1% of the population (Kempermann et al., 1997b), whereas in rats there is about twice as many surviving immature GCs (Snyder et al., 2009).


Dynamic functions of GABA signaling during granule cell maturation.

Dieni CV, Chancey JH, Overstreet-Wadiche LS - Front Neural Circuits (2013)

GABAergic innervation in adult neurogenesis. Cartoon depiction of the stages of GC maturation highlighting the sequence of interneuron innervation. Progressive stages of GC maturation are indicated by the blue cells. Select interneurons and their axonal targeting regions are indicated by the corresponding shaded areas (red, PV+ basket cells; green, Ivy/NG cells; orange, axo-axonal cells). The shift in function of GABA signaling from excitation to inhibition, and the sequence and modes of signaling from interneuron subtypes are indicated in the gradient bars below. The sequence of innervation by numerous other dentate interneuron subtypes [reviewed in Houser (2007)] is not yet known so not included. SGZ, subgranule zone; GCL, granule cell layer; ML, molecular layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539683&req=5

Figure 1: GABAergic innervation in adult neurogenesis. Cartoon depiction of the stages of GC maturation highlighting the sequence of interneuron innervation. Progressive stages of GC maturation are indicated by the blue cells. Select interneurons and their axonal targeting regions are indicated by the corresponding shaded areas (red, PV+ basket cells; green, Ivy/NG cells; orange, axo-axonal cells). The shift in function of GABA signaling from excitation to inhibition, and the sequence and modes of signaling from interneuron subtypes are indicated in the gradient bars below. The sequence of innervation by numerous other dentate interneuron subtypes [reviewed in Houser (2007)] is not yet known so not included. SGZ, subgranule zone; GCL, granule cell layer; ML, molecular layer.
Mentions: Adult neurogenesis encompasses the proliferation, differentiation, and maturation of new GCs that are continually added to the dentate. The continuum of neuronal development can be simplified into the stepwise progression of neural stem cells (Type I cells) into progenitors (Type II cells), differentiation of post mitotic newborn neurons, and the synaptic integration of immature GCs, with each stage exhibiting different physiological properties [Figure 1; reviewed by Mongiat and Schinder (2011)]. The absolute number of cells generated each day depends on rodent age and species, with estimates ranging between 2000 and 9000 under basal conditions (Kempermann et al., 1997b; Cameron and McKay, 2001). Adult generated neurons that survive the first few weeks following cell birth are likely to persist long term (Dayer et al., 2003), allowing adult generated neurons to accumulate over time, potentially achieving up to 10% of the total granule cell population (Lagace et al., 2007; Imayoshi et al., 2008). Yet the majority of newly generated cells undergo apoptosis within the week after division (Hayes and Nowakowski, 2002; Sierra et al., 2010), resulting in a population of immature neurons that is a small percentage of the total population of GCs. In young adult mice, it has been estimated that ~10–12 day-old GCs comprise about 3% of the population (Pugh et al., 2011) and 4-week old immature GCs comprise <1% of the population (Kempermann et al., 1997b), whereas in rats there is about twice as many surviving immature GCs (Snyder et al., 2009).

Bottom Line: Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region.Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages.We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.

ABSTRACT
The dentate gyrus is one of the few areas of the brain where new neurons are generated throughout life. Neural activity influences multiple stages of neurogenesis, thereby allowing experience to regulate the production of new neurons. It is now well established that GABA(A) receptor-mediated signaling plays a pivotal role in mediating activity-dependent regulation of adult neurogenesis. GABA first acts as a trophic signal that depolarizes progenitors and early post mitotic granule cells, enabling network activity to control molecular cascades essential for proliferation, survival and growth. Following the development of glutamatergic synaptic inputs, GABA signaling switches from excitatory to inhibitory. Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region. Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages. We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability.

No MeSH data available.


Related in: MedlinePlus