Distinct synaptic properties of perisomatic inhibitory cell types and their different modulation by cholinergic receptor activation in the CA3 region of the mouse hippocampus

Abstract

Perisomatic inhibition originates from three types of GABAergic interneurons in cortical structures, including parvalbumin-containing fast-spiking basket cells (FSBCs) and axo-axonic cells (AACs), as well as cholecystokinin-expressing regular-spiking basket cells (RSBCs). These interneurons may have significant impact in various cognitive processes, and are subjects of cholinergic modulation. However, it is largely unknown how cholinergic receptor activation modulates the function of perisomatic inhibitory cells. Therefore, we performed paired recordings from anatomically identified perisomatic interneurons and pyramidal cells in the CA3 region of the mouse hippocampus. We determined the basic properties of unitary inhibitory postsynaptic currents (uIPSCs) and found that they differed among cell types, e.g. GABA released from axon endings of AACs evoked uIPSCs with the largest amplitude and with the longest decay measured at room temperature. RSBCs could also release GABA asynchronously, the magnitude of the release increasing with the discharge frequency of the presynaptic interneuron. Cholinergic receptor activation by carbachol significantly decreased the uIPSC amplitude in all three types of cell pairs, but to different extents. M2-type muscarinic receptors were responsible for the reduction in uIPSC amplitudes in FSBC– and AAC–pyramidal cell pairs, while an antagonist of CB1 cannabinoid receptors recovered the suppression in RSBC–pyramidal cell pairs. In addition, carbachol suppressed or even eliminated the short-term depression of uIPSCs in FSBC– and AAC–pyramidal cell pairs in a frequency-dependent manner. These findings suggest that not only are the basic synaptic properties of perisomatic inhibitory cells distinct, but acetylcholine can differentially control the impact of perisomatic inhibition from different sources.

Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus

“…5 and 6; Table 3). This finding agrees well with data on physiological properties of these cells that are also more similar to PV-positive basket cells [fast-spiking properties with moderate accommodation and reliable transmission (Maccaferri et al, 2000;Szabó et al, 2010)]. …”

“…The mIPSC amplitude depends predominantly on the number of postsynaptic receptors that are proportional to the size of the synapses (Nusser et al, 1997), therefore, higher variability of the size of different synapses of CB 1 -positive somatic boutons may provide an anatomical basis for their highly variable quantal events. Several studies showed that synaptic connections between PV-positive basket cells and pyramidal cells are much more reliable than connections between CCK/CB 1 -positive basket cells and pyramidal cells, in the latter of which connection failures of synaptic transmission are frequent (Hefft and Jonas, 2005;Daw et al, 2009;Szabó et al, 2010). These observations are not easily explained, because boutons with larger synaptic area are generally considered to be more efficient and faithful (Pierce and Lewin, 1994;Holderith et al, 2012).…”

“…Furthermore, after high-frequency trains of presynaptic spikes, GABA release of CCK/CB 1 -positive basket cells is asynchronous with the presynaptic action potentials: latencies of postsynaptic responses are greatly variable, while PV-containing basket cells show highly synchronous release (Hefft and Jonas, 2005). In contrast to PV-positive basket cells that generates IPSCs in their postsynaptic pyramidal cells reliably with consistent amplitude, CCK/CB 1 -positive basket cells show large fluctuations of the postsynaptic response, and failures of synaptic transmission are more frequent (Hefft and Jonas, 2005;Daw et al, 2009;Szabó et al, 2010). In addition, CCK/CB 1 -positive basket cells have two nonoverlapping subgroups: one of them contain vasoactive intestinal polypeptide (VIP) (Acsády et al, 1996), whereas the other subgroup expresses vesicular glutamate transporter 3 (vGluT3) (Somogyi et al, 2004).…”

“…The third type of perisomatic interneuron is the axo-axonic cell, which is also PV-positive (Katsumaru et al, 1988) and releases GABA with precise timing and low failure rates similarly to PV-containing basket cells (Maccaferri et al, 2000;Szabó et al, 2010). While it is clear that basket cells inhibit their target neurons, the effect of axo-axonic cells is still debated and it can be either excitatory (Szabadics et al, 2006) or inhibitory (Glickfeld et al, 2009).…”

“…PV-positive basket and axoaxonic cells display fast spiking activity (Pawelzik et al, 2002) and probably are among the most active neurons in the cerebral cortex. In contrast to CB 1 -positive basket cells, firing of PV-positive perisomatic interneurons show high temporal precision (Hefft and Jonas, 2005;Daw et al, 2009;Szabó et al, 2010), which requires fast recovery of energetic and ionic balance in the synaptic terminal after individual spikes. These mechanisms demand more intense ATP production, which may require these larger mitochondria.…”