Developmental synaptic plasticity at the thalamocortical input to barrel cortex: mechanisms and roles

Abstract

The thalamocortical (TC) input to layer IV provides the major pathway for ascending sensory information to the mammalian sensory cortex. During development there is a dramatic refinement of this input that underlies the maturation of the topographical map in layer IV. Over the last 10 years our understanding of the mechanisms of the developmental and experience-driven changes in synaptic function at TC synapses has been greatly advanced. Here we describe these studies that point to a key role for NMDA receptor-dependent synaptic plasticity, a role for kainate receptors and for a rapid maturation in GABAergic inhibition. The expression mechanisms of some of the forms of neonatal synaptic plasticity are novel and, in combination with other mechanisms, produce a layer IV circuit that exhibits functional properties necessary for mature sensory processing.

Fig. 1

Electrophysiological recordings from neurons in layer IV barrel cortex in the thalamocortical (TC) slice preparation. (A) Schematic of the afferent pathway from the whiskers to barrel cortex. Inset: cytochrome oxidase C-stained tangential section through layer IV of barrel cortex showing the distinctive cytoarchitechnure. Reproduced from (Feldman and Brecht, 2005). (B) Cytochrome oxidase C-stained TC slice from 2 week old rat. The ventroposteriomedial nucleus of thalamus (VPM) that receives ascending sensory input from the whiskers, and the barrel cortex are indicated. Reproduced from (Petersen and Sakmann, 2000) (C) Unstained TC slice from P5 mouse as it appears in recording chamber during an electrophysiology experiment. Highlighted by the yellow box is a stellate cell (SC) filled with the fluorescent dye Alexa-594 during a whole-cell patch-clamp recording (Daw, Ashby and Isaac, unpublished). (D) High power image of the region highlighted in C, showing a whole-cell recording from an SC (patch electrode can be seen as the out of focus shadow in bottom left hand corner). (E) 2-photon image (flattened projection of Z-stack, contrast inverted for display) of an SC filled with Alexa-594 during patch clamp recording. (F) TC synaptic responses recorded during a whole-cell patch-clamp recording from an SC evoked by electrical stimulation of VPM thalamus. Top is an EPSC (voltage-clamp recording) and bottom EPSP (current clamp recording); responses collected in the same cell in response to the same stimulus (Daw, Ashby and Isaac, unpublished).

Fig. 2

Developmental profile for synaptic properties and long-term synaptic plasticity at TC synapses in layer IV barrel cortex. Each parameter is plotted as a % of the maximum value. The critical period for experience dependent plasticity in layer IV is also shown for comparison.

Fig. 3

Developmental profile of GABAergic inhibition in layer IV barrel cortex. GABA_A PSC E_rev is the reversal potential of the pharmacologically isolated GABA_A receptor-mediated PSC evoked in stellate cells (SCs) by local stimulation in layer IV/V border (measured using gramicidin perforated patch recordings). GABA PSC : AMPA EPSC ratio is the ratio of the TC EPSC and the disynaptic GABAergic PSC evoked in individual SCs in response to TC stimulation. IN-SC connection probability and IN-SC uIPSC (unitary IPSC) amplitude values are determined from paired recordings of fast spiking (FS) interneurons and SCs. IN EPSP : SC EPSP is the TC EPSP evoked in FS interneurons and SCs, and is determined from simultaneous recordings combined with thalamic stimulation. Inset top right: schematic showing the circuit for feed forward inhibition. All data from Daw, Ashby and Isaac, unpublished.