Switching between “On” and “Off” states of persistent activity in lateral entorhinal layer III neurons

Persistent neural spiking maintains information during a working memory task when a stimulus is no longer present. During retention, this activity needs to be stable to distractors. More importantly, when retention is no longer relevant, cessation of the activity is necessary to enable processing and retention of subsequent information. Here, by means of intracellular recording with sharp microelectrode in in vitro rat brain slices, we demonstrate that single principal layer III neurons of the lateral entorhinal cortex (EC) generate persistent spiking activity with a novel ability to reliably toggle between spiking activity and a silent state. Our data indicates that in the presence of muscarinic receptor activation, persistent activity following an excitatory input may be induced and that a subsequent excitatory input can terminate this activity and cause the neuron to return to a silent state. Moreover, application of inhibitory hyperpolarizing stimuli is neither able to decrease the frequency of the persistent activity nor terminate it. The persistent activity can also be initiated and terminated by synchronized synaptic stimuli of layer II/III of the perirhinal cortex. The neuronal ability to switch “On” and “Off” persistent activity may facilitate the concurrent representation of temporally segregated information arriving in the EC and being directed toward the hippocampus. © 2007 Wiley‐Liss, Inc.

[1]  O. Steward,et al.  Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat , 1976, The Journal of comparative neurology.

[2]  D. Penetar,et al.  Effects of cholinergic drugs on delayed match-to-sample performance of rhesus monkeys , 1983, Pharmacology Biochemistry and Behavior.

[3]  M. Witter,et al.  Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region , 1989, Progress in Neurobiology.

[4]  Rodrigo Andrade,et al.  Cell excitation enhances muscarinic cholinergic responses in rat association cortex , 1991, Brain Research.

[5]  P. Goldman-Rakic Cellular basis of working memory , 1995, Neuron.

[6]  D. D. Fraser,et al.  Cholinergic-Dependent Plateau Potential in Hippocampal CA1 Pyramidal Neurons , 1996, The Journal of Neuroscience.

[7]  T. Aigner,et al.  Release of cerebral acetylcholine increases during visually mediated behavior in monkeys , 1996, Neuroreport.

[8]  G Buzsáki,et al.  The hippocampo-neocortical dialogue. , 1996, Cerebral cortex.

[9]  Y. Miyashita,et al.  Formation of mnemonic neuronal responses to visual paired associates in inferotemporal cortex is impaired by perirhinal and entorhinal lesions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Alonso,et al.  Muscarinic modulation of the oscillatory and repetitive firing properties of entorhinal cortex layer II neurons. , 1997, Journal of neurophysiology.

[11]  R. Desimone,et al.  Object and place memory in the macaque entorhinal cortex. , 1997, Journal of neurophysiology.

[12]  H. Eichenbaum,et al.  Memory Representation within the Parahippocampal Region , 1997, The Journal of Neuroscience.

[13]  D. Amaral,et al.  Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat , 1998 .

[14]  D. Amaral,et al.  Perirhinal and postrhinal cortices of the rat: Interconnectivity and connections with the entorhinal cortex , 1998, The Journal of comparative neurology.

[15]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[16]  M. Hasselmo,et al.  Graded persistent activity in entorhinal cortex neurons , 2002, Nature.

[17]  A. Koulakov,et al.  Model for a robust neural integrator , 2002, Nature Neuroscience.

[18]  D. McCormick,et al.  Turning on and off recurrent balanced cortical activity , 2003, Nature.

[19]  B. Tahvildari,et al.  Synaptic activation patterns of the perirhinal-entorhinal inter-connections , 2004, Neuroscience.

[20]  M. Hasselmo,et al.  Persistence of Parahippocampal Representation in the Absence of Stimulus Input Enhances Long-Term Encoding: A Functional Magnetic Resonance Imaging Study of Subsequent Memory after a Delayed Match-to-Sample Task , 2004, The Journal of Neuroscience.

[21]  A. Alonso,et al.  Spike patterning by Ca2+-dependent regulation of a muscarinic cation current in entorhinal cortex layer II neurons. , 2004, Journal of neurophysiology.

[22]  M. Hasselmo,et al.  Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans , 2005, The Journal of Neuroscience.

[23]  M. Hasselmo,et al.  Cholinergic Deafferentation of the Entorhinal Cortex in Rats Impairs Encoding of Novel But Not Familiar Stimuli in a Delayed Nonmatch-to-Sample Task , 2005, The Journal of Neuroscience.

[24]  H. Sompolinsky,et al.  Bistability of cerebellar Purkinje cells modulated by sensory stimulation , 2005, Nature Neuroscience.

[25]  B. Tahvildari,et al.  Morphological and electrophysiological properties of lateral entorhinal cortex layers II and III principal neurons , 2005, The Journal of comparative neurology.

[26]  M. Hasselmo,et al.  Opinion TRENDS in Cognitive Sciences Vol.10 No.11 Mechanisms underlying working memory for novel information , 2022 .

[27]  J. Knierim,et al.  Hippocampal place cells: Parallel input streams, subregional processing, and implications for episodic memory , 2006, Hippocampus.

[28]  M. Hasselmo,et al.  Mechanism of Graded Persistent Cellular Activity of Entorhinal Cortex Layer V Neurons , 2006, Neuron.