The role of spiking and bursting pacemakers in the neuronal control of breathing

Abstract

Breathing is controlled by a distributed network involving areas in the neocortex, cerebellum, pons, medulla, spinal cord, and various other subcortical regions. However, only one area seems to be essential and sufficient for generating the respiratory rhythm: the preBötzinger complex (preBötC). Lesioning this area abolishes breathing and following isolation in a brain slice the preBötC continues to generate different forms of respiratory activities. The use of slice preparations led to a thorough understanding of the cellular mechanisms that underlie the generation of inspiratory activity within this network. Two types of inward currents, the persistent sodium current (I NaP ) and the calcium-activated nonspecific cation current (I CAN ), play important roles in respiratory rhythm generation. These currents give rise to autonomous pacemaker activity within respiratory neurons, leading to the generation of intrinsic spiking and bursting activity. These membrane properties amplify as well as activate synaptic mechanisms that are critical for the initiation and maintenance of inspiratory activity. In this review, we describe the dynamic interplay between synaptic and intrinsic membrane properties in the generation of the respiratory rhythm and we relate these mechanisms to rhythm generating networks involved in other behaviors.

Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons

“…6Aii). Since selective pharmacological block of I NaP has proven difficult (Ramirez et al, 2011;Richter et al, 2014), we evoked and isolated TTXsensitive steady-state currents by slow depolarizing voltage ramps (Carter et al, 2012). A TTX-sensitive current was first evident at ϳϪ75 mV and increased steeply with voltage (Fig.…”

The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

“…Moreover, within the mammalian nervous system, pacemaker neurons are not unique to the respiratory network, and are found in many areas of the CNS; some of these networks are concerned with complex higher functions (Brocard et al, 2013; Kolta et al, 2010; Llano and Sherman, 2009; Marcuccilli et al, 2010; Martell et al, 2010, 2012; Mrejeru et al, 2011; Ramcharan et al, 2005; Ramirez et al, 2004; Ziskind-Conhaim et al, 2010). Indeed, there is probably no region in the mammalian brain that does not contain pacemaker neurons (Ramirez et al, 2011). …”

“…However, the complement of these currents varies, and every individual neuron establishes a different dynamic balance of inward and outward currents, a principle that has been well documented for invertebrate neurons (Hudson and Prinz, 2010; Khorkova and Golowasch, 2007; Soofi et al, 2012; Temporal et al, 2012; Zhao and Golowasch, 2012). As a result, some neurons within the respiratory network are more bursting than others; some burst regularly, some are irregular, some discharge tonically, and some are silent (Carroll and Ramirez, 2013; Garcia et al, 2011; Koch et al, 2011; Ramirez et al, 2011, 2012; Viemari and Ramirez, 2006). Bursting depends more on the CAN current in some neurons (Fig.…”

“…Neuromodulators released endogenously can induce (Fig. 6A), inhibit, and significantly alter bursting properties in respiratory neurons (Dekin et al, 1985; Doi and Ramirez, 2010; Pena and Ramirez, 2002, 2004; Ptak et al, 2009; Ramirez et al, 2011, 2012; Tryba et al, 2008; Viemari et al, 2011; Fig. 6B).…”

Central Pattern Generators: Mechanisms of Operation and Their Role in Controlling Automatic Movements

“…Another example of a constitutive generator is provided by the respiratory CPG in vertebrates. Recently, signifi cant progress has been achieved in understanding the mechanism of respiratory rhythm generation in mammals [Feldman et al, 2013;Ramirez et al, 2011;Rybak et al, 2014;Smith et al, 2000]. We will restrict ourselves to a description of quiet respiration when the respiratory center operates in the regime of a monophasic CPG generating only the inspiratory phase of the cycle, whereas the expiratory phase is passive.…”