GABA(B)-receptor-mediated inhibition in developing mouse ventral posterior thalamic nucleus
R A Warren1, P Golshani, E G Jones
1Centre de Recherche Fernand-Seguin, Montreal, Quebec, Canada.
Insights
This study reveals that both early gamma-aminobutyric acid-A (GABA(A)) and late GABA(B) inhibitory postsynaptic potentials (IPSPs) are present in the developing mouse thalamus. These distinct IPSPs exhibit independent developmental trajectories in the ventral posterior nucleus.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurophysiology
Background:
- The thalamus plays a crucial role in sensory processing and relay.
- Postnatal development of thalamic circuits involves complex changes in neuronal excitability and synaptic transmission.
- Inhibitory postsynaptic potentials (IPSPs) are critical for shaping neuronal activity and circuit function.
Purpose of the Study:
- To investigate the developmental characteristics of inhibitory postsynaptic potentials (IPSPs) in the ventral posterior nucleus (VP) of the mouse thalamus.
- To differentiate the roles and developmental timelines of GABA(A) and GABA(B) receptor-mediated IPSPs.
- To understand the maturation of inhibitory neurotransmission in the early postnatal thalamus.
Main Methods:
- In vitro electrophysiological recordings of IPSPs in mouse thalamic slices from postnatal day 1 to 17.
- Pharmacological manipulation using bicuculline (GABA(A) antagonist) and 2-hydroxysaclofen (GABA(B) antagonist).
- Analysis of IPSP kinetics, reversal potentials, and developmental changes.
Main Results:
- An early GABA(A)-mediated IPSP was consistently observed in VP neurons.
- A late GABA(B)-mediated IPSP was identified and characterized, becoming more apparent with bicuculline application.
- The late IPSP showed significant developmental changes, including a marked shortening in duration between P1 and P10, while its reversal potential remained constant.
- The early IPSP's reversal potential became more negative during development, unlike the late IPSP.
Conclusions:
- Both GABA(A) and GABA(B) mediated IPSPs are established early in postnatal thalamic development.
- These two distinct inhibitory pathways mature independently, suggesting unique regulatory mechanisms.
- Understanding these developmental trajectories is key to comprehending the formation of sensory processing circuits in the thalamus.
Abstract:
Inhibitory postsynaptic potentials (IPSPs) generated by activation of the thalamic reticular nucleus (RTN) were recorded in neurons of the ventral posterior nucleus (VP) in vitro in slices from mice aged postnatal day (P)1-P17. An early IPSP peaking 41 +/- 2.5 (SE) ms after electrical stimulation of the internal capsule or RTN was found in 96% of VP neurons. This early IPSP was blocked by bicuculline, showing its dependence on gamma-aminobutyric acid-A (GABA(A)) receptors. A late IPSP peaking 357 +/- 27 ms after the stimulus was observed in 22% of VP neurons in control medium but was uncovered in 38% of neurons when bicuculline was added. The late IPSP was blocked by addition of a GABA(B) antagonist, 2-hydroxysaclofen, to the medium (n = 7); it had a reversal potential of -98 +/- 1.3 mV, 14 mV negative to the early component. In contrast to the early IPSP, whose reversal potential became more negative during postnatal development, the reversal potential of the late IPSP remained constant throughout the postnatal period studied. The most significant change in the late IPSP was shortening in duration, with reduction in latency-to-peak by >400 ms, between P1 and P10. No changes of comparable magnitude were observed in the duration of the earlier GABA(A) response. These results show that both GABA(A) and GABA(B) IPSPs are present very early in the postnatal thalamus and that their characteristics evolve along independent paths during postnatal development.
