Neocortical disynaptic inhibition requires somatodendritic integration in interneurons - PubMed (original) (raw)

Neocortical disynaptic inhibition requires somatodendritic integration in interneurons

Court Hull et al. J Neurosci. 2009.

Abstract

In his theory of functional polarity, Ramon y Cajal first identified the soma and dendrites as the principal recipient compartments of a neuron and the axon as its main output structure. Despite notable exceptions in other parts of the nervous system (Schoppa and Urban, 2003; Wässle, 2004; Howard et al., 2005), this route of signal propagation has been shown to underlie the functional properties of most neocortical circuits studied so far. Recent evidence, however, suggests that neocortical excitatory cells may trigger the release of the inhibitory neurotransmitter GABA by directly depolarizing the axon terminals of inhibitory interneurons, thus bypassing their somatodendritic compartments (Ren et al., 2007). By using a combination of optical and electrophysiological approaches, we find that synaptically released glutamate fails to trigger GABA release through a direct action on GABAergic terminals under physiological conditions. Rather, our evidence suggests that glutamate triggers GABA release only after somatodendritic depolarization and action potential generation at GABAergic interneurons. These data indicate that neocortical inhibition is recruited by classical somatodendritic integration rather than direct activation of interneuron axon terminals.

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Figures

Figure 1.

Increasing glutamate release from individual pyramidal cells with cesium dialysis promotes disynaptic inhibition. A, IPSCs can be generated between pyramidal cell pairs in L2/3 with a cesium-based internal solution. Left, A paired recording from two nearby L2/3 pyramidal cells with a cesium internal solution in both cells. A brief depolarizing voltage step (40 mV for 1 ms) applied to one pyramidal cell (top) yields an unclamped spike (or “action current”). This spike produces a large IPSC in the other pyramidal cell (bottom; 0 mV). Right, Summary data of the latencies and amplitudes of IPSCs generated with cesium internal solutions. IPSCs were observed in 16 of 69 (23%) total recordings with a cesium internal. B, Repatching with a cesium-based internal solution generates IPSCs between pyramidal cell pairs. Left, A pair of pyramidal cells, in which one cell contains a potassium internal (top) and the other contains a cesium internal (bottom; 0 mV). Action potentials triggered in the pyramidal cell filled with potassium do not produce IPSCs in the pyramidal cell filled with cesium. Right, When the same pyramidal cell is repatched with a cesium-based internal solution, action currents (as in A) now produce IPSCs in the other pyramidal cell. C, Repatching pyramidal cells with a cesium-based internal solution doubles the size of EPSPs onto FS interneurons. Left, Paired recordings performed between a layer 2/3 pyramidal cell and an FS interneuron. The pyramidal cell is first patched with a potassium internal solution (green) and subsequently repatched with a cesium internal solution (black, as in A). Right, Summary data. Switching from a potassium- to a cesium-based internal solution produced a 2.2-fold increase in the EPSPs recorded in FS interneurons (n = 8). D, The increase in FS interneuron EPSPs does not result from the voltage-clamp paradigm per se. Left, EPSP generated in an FS interneuron by triggering a spike (black) or an action current (blue) in the presynaptic pyramidal cell recorded in the current clamp or voltage clamp configuration, respectively. Right, Summary data. Note the lack of difference in the amplitude of the EPSP evoked with either recording configuration. ss, Somatosensory.

Figure 2.

Strong glutamate release from pyramidal cells does not drive action potential-independent disynaptic inhibition. A, Brief flashes of blue light to ChR2-expressing L2/3 pyramidal cells drives neurotransmitter release onto neighboring ChR2-negative L2/3 cells. Cells exhibit both glutamatergic (V h = −70 mV) and disynaptic GABAergic (V h = 0 mV) responses (note temporal delay in inset) in the absence of TTX (left), but only direct glutamatergic responses when action potentials are blocked and synaptic release is facilitated by the potassium channel blocker 4-AP. B, Example experiment showing the amplitude of the postsynaptic current before and during TTX application, and in the additional presence of 4-AP. The cell is held at −70 mV except as indicated. C, Left, Amplitude of postsynaptic currents recorded at −70 and 0 mV in the presence of TTX and 4-AP in layer 2/3 of somatosensory cortex (mean at −70 mV, −653 ± 75 pA; at 0 mV, −5 ± 5 pA; n = 7). Right, Currents for cells recorded in visual cortex (mean at −70 mV, −780 ± 156 pA; at 0 mV, 4 ± 3 pA; n = 13).

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Neocortical disynaptic inhibition requires somatodendritic integration in interneurons - PubMed (original) (raw)