TRANSMISSION ACROSS FIRST SYNAPSE OF THE BAROREFLEX

Baroreflexes are an important part of the neural regulation of the
cardiovascular system, but the cellular basis of the central nervous
system (CNS) contribution to these reflexes is poorly understood. The area
of densest innervation by the baroreceptor afferents is in the dorsomedial
portion of the nucleus of the tractus solitarius (NTS). Reflex studies and
extracellular recordings of neuron activity from the medulla suggest that
the NTS is a key area where incoming afferent information is transformed
before going on to other brain areas involved in the control of heart rate
and blood pressure. A number of studies suggest that the properties of NTS
neurons may be altered during hypertension. The proposed work will focus
on characterizing the cellular basis of synaptic transmission at the
afferent-NTS synapse. CNS studies are hampered by difficulties in gaining
physical access to these small neurons and in recording conditions in the
intact brain. Thus most of what we know about NTS neurons is based on
extracellular activity recordings which provide limited information. An in
vitro longitudinal slice preparation of the rat medulla has been developed
to study medial NTS neurons using intracellular recordings to measure
responses to afferent synaptic input. The longitudinal slice offers
important advantages by preserving both lengthy sections of the solitary
tract and key anatomical landmarks for microelectrode placement and by
providing precise of control experimental conditions such as drug
concentrations. Electrical stimulation of afferent axons will be used to
evoke postsynaptic responses. Several key issues in afferent-NTS synaptic
transmission will be examined including: 1) the mechanism of frequency
dependent depression of synaptic responses and the influence of
intermittent or burst modes of stimulation, 2) the identity of the primary
excitatory transmitter and its postsynaptic receptor type, 3) the
potential role and identity of inhibitory transmitters in synaptic
modulation, and 4) possible changes in primary excitatory transmission or
its modulation in genetic hypertension. Primary candidate
neurotransmitters include glutamate, substance P, gamma-aminobutyric acid,
and norepinephrine. Dual marking (with transganglionic transport of
horseradish peroxidase in aortic baroreceptor nerves and intracellular dye
injection) will be used to identify neurons characterized
electrophysiologically which received cardiovascular afferent inputs.
Immunocytochemistry will identify neurotransmitters localized on cell
bodies or processes. These studies should provide important new
information concerning the CNS mechanisms involved in a critical step of
reflex autonomic control of the hear and blood pressure during normal and
pathological states such as hypertension.