LM) and neurogliaform cells [30]. Interestingly, all domains of pyramidal cells are

LM) and neurogliaform cells [30]. Interestingly, all domains of order HM61713, BI 1482694 pyramidal cells are innervated by a group of interneuron types expressing the calcium-binding protein parvalbumin (PV). In addition, all domains, except the axon initial segment, are also innervated by a distinct set of cholecystokinin-expressing (CCK) GABAergic cells. The PV- and CCK-expressing families of interneurons differ in their biophysical parameters, synaptic connectivity, neurochemical components and in vivo firing patterns [31,38,41]. A set of six types of GABAergic cell, in addition to innervating pyramidal cells and interneurons in the hippocampus, also project to extrahippocampal areas such as the septum, subiculum, indusium griseum, retrosplenial cortex and the entorhinal cortex [37,42,43]. Interneurons are purchase Anisomycin interconnected in complex ways [44], and there is a set of specialized interneurons innervating other interneuron types mostly or exclusively [29]. It is not yet clear whether all types of CA1 pyramidal cell receive input from all of the interneurons innervating pyramidal cells.rstb.royalsocietypublishing.org Phil. Trans. R. Soc. B 369:2. Theta oscillation and interneuron firingSeveral models of the spatial navigation system suggest a role for rhythmic change in principal cell activity at theta frequencies [45 ?9]. Indeed, the frequency and amplitude of local field potential (LFP) theta oscillations are strongly modulated by the speed of movement, with speed positively correlated to theta frequency [50,51]. During theta oscillations, GABAmediated inhibition rhythmically changes in pyramidal cells [52 ?6]. The overall population of active pyramidal cells fires the most action potentials per theta cycle just after the trough of the LFP theta cycle recorded in the pyramidal layer, indicating the highest excitability [57,58]. When the animal enters the place field of a given pyramidal place cell, the cell starts firing close to the peak of the extracellular theta field potential [58], when the overall population of pyramidal cells are strongly inhibited. As the animal traverses the place field, place cells fire with a systematic backward phase shift (phase precession) in their coupling to the theta LFP on consecutive theta cycles. Intracellular recordings show that place cells discharge when the theta-rhythmically changing membrane potential is most depolarized [59,60] and within the place field the intracellular oscillation is faster than the extracellular LFP theta oscillation [60]. The firing of simultaneously recorded place cells and interneurons can be either positively or negatively correlated [10,61,62] indicating diverseother isocortexinternal and external environment entorhinal cortex CArstb.royalsocietypublishing.orgstratum lacunosum moleculare CCK cellsdentate gyrusivy cellbistratified cellPV basket cellaxoaxonic cellCA3 pyramidal cells stratum radiatumPhil. Trans. R. Soc. B 369:stratum pyramidale subicular complex subcortical areas theta PV pyramidal basket cells cells 0.04 0.05 0 0.2 0 0.2 firing probability 0 0.4 0 0.1 0 0.02 0 0.08 0 0?360?theta phase 720?0 0.4 0 0.2 0 0.1 0 0.3 0 0.1 0 0.04 0 ? 0 1 normalized time O-LM cell ripples stratum oriens septum GABA ACh gamma depth of modulation (r) 0.2 0 0.2 0 0.2 0 0.2 0 0.2 0 0.2 0 0.2Figure 1. Schematic of the spatial and temporal relationships between pyramidal cells and eight types of GABAergic interneuron in the CA1 area. Top: the main synaptic connections of pyramidal cells (red, middle), three.LM) and neurogliaform cells [30]. Interestingly, all domains of pyramidal cells are innervated by a group of interneuron types expressing the calcium-binding protein parvalbumin (PV). In addition, all domains, except the axon initial segment, are also innervated by a distinct set of cholecystokinin-expressing (CCK) GABAergic cells. The PV- and CCK-expressing families of interneurons differ in their biophysical parameters, synaptic connectivity, neurochemical components and in vivo firing patterns [31,38,41]. A set of six types of GABAergic cell, in addition to innervating pyramidal cells and interneurons in the hippocampus, also project to extrahippocampal areas such as the septum, subiculum, indusium griseum, retrosplenial cortex and the entorhinal cortex [37,42,43]. Interneurons are interconnected in complex ways [44], and there is a set of specialized interneurons innervating other interneuron types mostly or exclusively [29]. It is not yet clear whether all types of CA1 pyramidal cell receive input from all of the interneurons innervating pyramidal cells.rstb.royalsocietypublishing.org Phil. Trans. R. Soc. B 369:2. Theta oscillation and interneuron firingSeveral models of the spatial navigation system suggest a role for rhythmic change in principal cell activity at theta frequencies [45 ?9]. Indeed, the frequency and amplitude of local field potential (LFP) theta oscillations are strongly modulated by the speed of movement, with speed positively correlated to theta frequency [50,51]. During theta oscillations, GABAmediated inhibition rhythmically changes in pyramidal cells [52 ?6]. The overall population of active pyramidal cells fires the most action potentials per theta cycle just after the trough of the LFP theta cycle recorded in the pyramidal layer, indicating the highest excitability [57,58]. When the animal enters the place field of a given pyramidal place cell, the cell starts firing close to the peak of the extracellular theta field potential [58], when the overall population of pyramidal cells are strongly inhibited. As the animal traverses the place field, place cells fire with a systematic backward phase shift (phase precession) in their coupling to the theta LFP on consecutive theta cycles. Intracellular recordings show that place cells discharge when the theta-rhythmically changing membrane potential is most depolarized [59,60] and within the place field the intracellular oscillation is faster than the extracellular LFP theta oscillation [60]. The firing of simultaneously recorded place cells and interneurons can be either positively or negatively correlated [10,61,62] indicating diverseother isocortexinternal and external environment entorhinal cortex CArstb.royalsocietypublishing.orgstratum lacunosum moleculare CCK cellsdentate gyrusivy cellbistratified cellPV basket cellaxoaxonic cellCA3 pyramidal cells stratum radiatumPhil. Trans. R. Soc. B 369:stratum pyramidale subicular complex subcortical areas theta PV pyramidal basket cells cells 0.04 0.05 0 0.2 0 0.2 firing probability 0 0.4 0 0.1 0 0.02 0 0.08 0 0?360?theta phase 720?0 0.4 0 0.2 0 0.1 0 0.3 0 0.1 0 0.04 0 ? 0 1 normalized time O-LM cell ripples stratum oriens septum GABA ACh gamma depth of modulation (r) 0.2 0 0.2 0 0.2 0 0.2 0 0.2 0 0.2 0 0.2Figure 1. Schematic of the spatial and temporal relationships between pyramidal cells and eight types of GABAergic interneuron in the CA1 area. Top: the main synaptic connections of pyramidal cells (red, middle), three.