Modulation of the input/output function of rat piriform cortex pyramidal cells

“The spiking response of cortical neurons to sensory input is further enhanced by muscarinic receptors causing a decrease in potassium conductances, including resting conductances (Krnjevic et al, 1971; Cole and Nicoll, 1984; Barkai and Hasselmo, 1994; Gulledge et al, 2009), the Cholinergic neuromodulation ME Hasselmo…”

“…enhances thalamic afferent input, while muscarinic suppression reduces excitatory recurrent processing in cortex. structures (McCormick and Prince, 1986) as well as the piriform cortex (Tseng and Haberly, 1989; Barkai and Hasselmo, 1994) and hippocampal region CA1 (Madison and Nicoll, 1984).”

“The mean increase in the IPSP, measured >20 min after the tetanus, was 28 t- 6%.”

“This gave a reasonable simplified representation of the output characteristics of cortical pyramidal cells in response to intracellular current injection (Barkai and Hasselmo, 1994).”

“, 1963), hippocamIn order to record from identified hypocretin neurons, transgenic pal neurons (Madison and Nicoll, 1984), neurons from mice were generated that expressed enhanced green fluorescent piriform cortex (Barkai and Hasselmo 1994), and some protein selectively in hypocretin neurons.”

“We focused on its modulation of neuronal response to time-varying inputs, in contrast to previous modeling work (Douglas et al., 1995; Barkai and Hasselmo, 1994 ), where IAHP was incorporated as a static gain control.”

“choline depolarizes cortical pyramidal cells, bringing them closer to firing threshold [61,62].”

“Generation of action potentials in simulated neurons depended upon the fast voltage-dependent sodium current (I,,) and the delayed rectifier potassium current (I,,,,,), with parameters provided in a previous publication (Barkai and Hasselmo, 1994).”

“At the same time, acetylcholine further enhances the response to feedforward input by causing post-synaptic depolarization of neurons (Barkai and Hasselmo, 1994; Benardo & Prince, 1982), suppression of neuronal adaptation (Barkai & Hasselmo, 1994) and suppression of feedback inhibition (Patil & Hasselmo, 1999).”

“In mammals, SFA has been observed in rodent motoneurons (Granit et al. 1963; Sawczuk et al. 1995), hippocampal CA1 pyramidal cells (Lancester and Nicoll 1987; Madison and Nicoll 1984), and pyramidal cells of the piriform cortex (Barkai and Hasselmo 1994).”

“Cholinergic agonists also suppress adaptation of pyramidal cells in piriform cortex [74] and cingulate cortex, by blocking the slow after-hyperpolarization that follows a train of action potentials and blocking the M-current [75].”

“Nonlinear Interaction between Shunting and Adaptation”

“Tonic-like cholinergic effects generated by phasic mAChR stimulation Although studies examining cholinergic modulation of neuron excitability have often used tonic stimulation with bath-applied agonists such as carbachol (Schwindt et al., 1988; Williams and Constanti, 1988; Halliwell, 1989; Barkai and Hasselmo, 1994;…”

“A model of CA1 network-mediated pattern recognition can be examined for changes induced by NMDAR-antagonists based on realistic biophysical, synaptic, and anatomical properties (Traub et al, 1993; Barkai and Hasselmo, 1994; Hasselmo, 1995).”

“…a noninactivating voltage-dependent potassium current (IK−M ), a calcium-dependent potassium current (IK−AH P), and a high-threshold voltage activated calcium current (ICa) similar to those in other pyramidal cell models (Barkai and Hasselmo, 1994; Traub et al., 1991; Pinsky and Rinzel, 1994).”

“Although this concept has received strong support mainly from in vitro studies ( Barkai & Hasselmo, 1994; Pitler & Alger, 1992), behavioral evidence for the suggested role of ACh levels on consolidation and mem-”

“Cholinergic modulation of synaptic potentials (Hasselmo et al., 1992; Hasselmo & Barkai, 1995; Linster et al., 1999; Patil et al., 1998) and neuronal adaptation (Barkai & Hasselmo 1994) could limit spread of the induced synaptic plasticity, further enhancing specificity of the stored pattern.”

“…a reduction in pyramidal cell afterhyperpolarization and spiking adaptation to current steps, and thus a potential increase in signal-to-noise ratios (Barkai and Hasselmo 1994; Saar et al. 2001); and (3) modulation of long-term potentiation of association fiber synapses (Hasselmo and Barkai 1995).”

“Application of acetylcholine agonists to pyramidal cells in vitro reduces both AHP (Schwindt et al., 1988) and spike firing adaptation (Barkai and Hasselmo, 1994).”

“…electrical properties of SP cells have been described previously (Haberly and Bower, 1984; Hasselmo and Bower, 1992; Gellman and Aghajanian, 1993; Barkai and Hasselmo, 1994; Kapur et al., 1997; Protopapas and Bower, 2001; Franks and Isaacson, 2005, 2006), but in many of these cases it is even…”

“For comparison, Barkai and Hasselmo (1994) observed two to three times the control spiking response following the introduction of acetylcholine.”

“Specifically, acetylcholine depolarizes both pyramidal and inhibitory neurons, increasing their spontaneous and stimulus-evoked spiking (Barkai and Hasselmo, 1994; Tseng and Haberly, 1989a,b).”

“Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.941510.”

“There is also a high-threshold voltage-activated calcium current (ICa) similar to those in other pyramidal cell models ( Barkai & Hasselmo, 1994; Traub, Wong, Miles, & Michelson, 1991; Pinsky & Rinzel, 1994).”

“Acetylcholine causes a depolarization of the membrane potential of pyramidal cells (Tseng and Haberly, 1989; Barkai and Hasselmo, 1994) and interneurons (Gellman and Aghajanian, 1993), and suppresses the spike frequency accommodation of pyramidal cells (Tseng and Haberly, 1989; Barkai and Hasselmo,…”

“In slices, piriform cortex pyramidal cells can generally be classified into strongly adapting or weakly adapting cells, depending on their response to long constant depolarizing current pulses (Barkai & Hasselmo, 1994).”

“This means that the firing patterns became more sustained and more regular when ACh was applied, indicative of reduced spike frequency adaptation probably mediated by muscarinic mechanisms (McCormick & Prince, 1986; Barkai & Hasselmo, 1994; Cox et al., 1994; Morton & Davies, 1997; Tang et al., 1997).”

“In addition, ACh has been shown to enhance activitydependent synaptic modification (Hasselmo & Barkai, 1995), which may result from suppression of the normal adaptation of firing by pyramidal cells to a sustained depolarizing current injection ( Barkai & Hasselmo, 1994 ), which would enhance both pre- and postsynaptic…”

“…inhibitory circuits between pyramidal cells and GABAergic basket cells are thought to be responsible for gamma oscillation generation in the APC, and are also under the control of the neuromodulatory system (Gellman and Aghajanian, 1993; Barkai and Hasselmo, 1994; Hasselmo and Barkai, 1995).”

“More recently, the importance This further supports our hypothesis that the laminar supof cholinergic modulation in associative memory function pression of inhibition caused by carbachol facilitates this has been shown theoretically (Barkai and Hasselmo 1994; type of potentiation.”

“…the conductance densities of the muscarinic potassium current IM and the Ca 2 -dependent potassium current IKCa to zero, since these two conductances underlie AHP responses and are blocked by muscarinic agonists (Madison et al., 1987; Barkai and Hasselmo, 1994; Wang, 1999; Pressler et al., 2007).”

“Four hundred micrometer coronal brain slices were cut as previously described (Barkai and Hasselmo, 1994) and kept in oxygenated (95% O2 plus 5% CO2) Ringer’s solution (in mM: NaCl 124, KCl 3, MgSO4 2, NaH2PO4 1.”

“The major effort in this direction has been made by Hasselmo and colleagues [4, 5, 30-34].”

“The simulations predict a direct and positive relation between the extent of prediction and the degree of firing rate adaptation, and the latter might be manipulated, e.g., by acting on potassium channels or on the cholinergic system ( Barkai and Hasselmo, 1994 ).”

“The induction of Hebbian synaptic modification could also be enhanced by muscarinic enhancement of postsynaptic spiking activity due to direct depolarization of cortical pyramidal cells (Cole and Nicoll, 1984; Barkai and Hasselmo, 1994) as well as suppression of spike frequency accommodation (Madison and Nicoll, 1984;…”

“1999) and regulates adaptation of pyramidal cell firing to step depolarization (Barkai and Hasselmo 1994).”

“The model of Brunel (1996) and related work by Amit (see Amit (1999) for an overview) study how recurrent connections between IT neurons develop during repeated presentations of stimuli, but the set of IT neurons activated by feedforward input to IT cortex does not change.”

“This enhanced excitability plays a key role in maintaining the cortical network in a “learning mode” in which memories can be stored rapidly and efficiently (Barkai and Hasselmo, 1994; Saar and Barkai, 2003).”

“…approach, we do not consider how arousal - related signals, such as cholinergic modulation for example, affect the physiological properties of pyramidal cells, such as excitability (62, 63), spike frequency adaptation (64–66) and modulation of both GABAergic and glutamatergic transmission (67).”

“Disruption of normal aPCX association fiber synaptic transmission and plasticity, for example by disrupting cholinergic input (Barkai and Hasselmo, 1994; Patil et al., 1998), impairs olfactory perceptual learning at both the cortical (Wilson, 2001; Linster et al.”

“These connections were inhibitory and had fast time courses representing GABAA receptors.”

“For example, serotonin helps reduce fear processing in the amygdala via GABA modulation but it exerts an excitatory effect on cortical brain activity when it binds to 5-HT2A serotonin receptors on layer V pyramidal neurons (Barkai and Hasselmo, 1994; Aghajanian and Marek, 1999).”

“…with discrete end values, including spatial orientation, sensory pattern recognition, categorical perceptual judgments, and execution of movement trajectories (Lukashin et al. 1996; Wyttenbach et al. 1996; Bartlett and Sejnowski 1998; Fdez Galan et al. 2004; Wills et al. 2005; Wong and Wang 2006).”

“Under control conditions, most pyramidal neurons rarely fire action potentials 200 ms after stimulus onset ( Barkai and Hasselmo, 1994 ).”

“(2013), cholinergic modulation in the piriform cortex switches the dynamics of the network between learning (ACh ON) and recalling (ACh OFF) modes (Hasselmo and Bower, 1992; Barkai and Hasselmo, 1994; Hasselmo and Barkai, 1995).”

“RSNP cells had action potentials with a fairly high spike adaptation ratio (0.60 ± 0.02, Table 1 and Fig.”

“In the piriform cortex, acetylcholine arising from the horizontal limb of the diagonal band selectively modulates intra-cortical association fiber synapses and pyramidal cell excitability [3].”

“In the case of pyramidal neurons, the effects, broadly speaking, can collectively be described as “increasing excitability” (Schwindt et al., 1988; McCormick, 1993; Barkai and Hasselmo, 1994; Fraser and MacVicar, 1996; Haj-Dahmane and Andrade, 1996, 1998; Klink and Alonso, 1997).”

“This is true (Barkai & Hasselmo, 1994) over the range of firing frequencies observed in vivo (O’Keefe & Recce, 1993; Skaggs et al., 1996).”

“Conversely, septal modulation can enhance pyramidal cell excitability in the hippocampus by suppressing adaptation (Barkai & Hasselmo, 1994; Madison, Lancaster, & Nicoll, 1987) and enhancing synaptic plasticity (Hasselmo & Barkai, 1995; Huerta & Lisman, 1993).”

“(11) The neural gain, on the other hand, is increased by acetylcholine (Barkai and Hasselmo 1994; Disney et al. 2007; Gulledge et al. 2009; Soma and Shimegi 2016), serotonin (Zhang and Arsenault 2005), and noradrenalin (McCormick 1989; Timmons et al. 2004).”

“…synaptic transmission (Hasselmo & Schnell, 1994), enhancement of pyramidal cell excitability through suppression of cur rents underlying adaptation (Barkai & Hasselmo, 1994; Madison, Lancaster, & Nicoll, 1987), and enhancement of synaptic modification (Hasselmo & Barkai, 1995; Huerta & Lisman,…”

“But changes in ACh tone also change the gain response of neurons (Barkai and Hasselmo, 1994; Soma et al., 2012, 2013).”

“Hasselmo and colleagues have produced a number of studies of cholinergic neuromodulation in both abstracted and realistic network models (Hasselmo and Wyble, 1996; Hasselmo et al., 1996; Hasselmo and Barkai, 1995; Hasselmo et al., 1995; Barkai et al., 1994; Barkai and Hasselmo, 1994; Hasselmo and Schnell, 1994).”

“These mainly consist of glutamatergic principal cells respectively providing the input and output communication pathways of Ammon ’ s Horn (Barkai & Hasselmo, 1994; Hestrin et al., 1990; Wang et al., 2006; Yang et al., 1996).”

“This description and associated computational models portray ACh as a promoter of sensory processing by decrease in a single AHP current either by lumping distinct AHP currents together or neglecting two of the three currents (Barkai and Hasselmo, 1994; Cox et al., 1997; Wang et al., 2003; Soto et al., 2006; Grossberg…”

“Hasselmo and colleagues (Barkai and Hasselmo 1994; Hasselmo and Bower 1992; Hasselmo and Cecik 1996) proposed a specific role for cholinergic modulation in the PC.”

“…of the neurons are not represented explicitly, and more complex neural networks using Hodgkin–Huxley-like neurons and realistic synaptic connectivity can be used to try to overcome these limitations (Wilson and Bower 1992, Barkai and Hasselmo 1994, Barkai et al 1994, Hasselmo and Barkai 1995).”

“Accordingly, muscarinic agonists suppress adaptation in cortical pyramidal cells recorded in brain slices by blocking Kþ currents (Barkai and Hasselmo, 1994; McCormick and Prince, 1986; for review see Krnjevic, 2004).”

“3B) resembles that shown previously for piriform cortex pyramidal neurons (Barkai & Hasselmo, 1994; Saar & Barkai, 2003).”

“The model of calcium dynamics is based on previous models (Anwar et al. 2010; Barkai and Hasselmo 1994; Canavier et al. 2007; Wang et al. 2003; Wilson et al. 2004).”

“In the presence of carbachol (10 mM), the adaptation was reduced in agreement with previous studies in entorhinal cortex [29] as well as other cortical structures [30,31].”

“…response to afferent input by muscarinic cholinergic reductions of postsynaptic potassium conductances including the leak conductance, the M-current (Adams and Brown 1982), and the calcium-dependent potassium conductance K(AHP) (Madison, Lancaster, and Nicoll 1987; Barkai and Hasselmo 1994).”

“Both increases and decreases in AHP conductances could lend themselves to experimental tests (Barkai and Hasselmo 1994; Suppes et al. 1985).”